JPS5980692A - Novel anthracyclineglycosides - Google Patents

Abstract

(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to anthracycline glycosides, processes for their production, drugs containing the glycosides, and uses of the glycosides.

The anthracycline glycosides provided by the present invention have the general formula: R is a hydrogen atom, a lower alkyl, an aryl or an aryl-(lower alkyl) group, a 5- or 6-membered heteroatom in which the heteroatom is nitrogen, oxygen or sulfur; represents a teloaromatic group or a group of the formula -(C112)n-COR' (α), R' represents a hydroxy, lower alkoxy, amino, lower alkylamino, di(lower alkyl)amine or arylamino group, n represents an integer of 1 to 4, n/ represents an integer of 2 to 10, each of R1 and R2 represents a hydrogen atom, or R1
and Rt represent a hydrogen atom, and the other represents a hydroxy, lower alkoxy or benzyloxy group, and X is a compound of the formula (1) and a pharmaceutically acceptable acid addition salt thereof .

As used herein, the term "lower alkyl"
alone or in combination, e.g. aryl-(lower alkyl)
, lower alkylamino and di(lower alkyl)amines, straight-chain or branched alkyl groups containing 1 to 5 carbon atoms, such as methyl, ethyl, n-propyl,
It means isopropyl, n-butyl, t-7'tyl, n-pentyl, etc. The term "aryl", alone or in combination, e.g. aryl-(lower alkyl) and arylamino, refers to a phenyl group or a substituted phenyl group, i.e., e.g. lower alkyl, lower alkoxy, -
It means a phenyl group having one or more substituents selected from rogene, nitro, amino, carboxy, hydroxy, cyan, and trifluoromethyl. Examples of phenyl groups thus substituted are p-tolyl, p-methoxyphenyl, m-hydroxyphenyl, O-nitrophenyl, f'-nitrophenyl, p-chloropheny/l/,
2,4-') chlorophenyl, etc. Aryl (
Examples of lower alkyl groups include benzyl, p-chlorobenzyl and 2-phenylethyl t[-J',
Anilino can be mentioned as an example of an arylamino group. Examples of 5- and 6-membered heteroaromatic groups represented by R are pyridyl, chenyl, and the like. The term "lower alkoxy" refers to lower alkyl ether groups in which lower alkyl is as previously defined; examples of such lower alkoxy groups are methoxy, ethoxy, n-propoxy, isopropoxy, and the like. Examples of lower alkylamino groups are methylamino, ethylamino, n-propylamino, etc., and examples of di(lower alkyl)amino groups are dimethylamino, diethylamino, etc. The term "/-logen" means fluorine, chlorine, bromine or iodine.

An interesting group of compounds of formula (2) is a group in which R is a lower alkyl, aryl or aryl group, a 5- or 6-membered heteroaromatic group in which the petro atom is nitrogen, oxygen or sulfur, or a 5- or 6-membered heteroaromatic group of the formula ( α) represents a group of R1 and R
2 each represents a hydrogen atom, or one of R1 and R2 represents a hydrogen atom and the other represents a hydroxy or methoxy group.

A preferred group of compounds of formula I consists of compounds in which R represents an aryl group, especially phenyl. Analogously to the compounds of formula I in which X represents a group of formula (i) or (11) above, also R
Preference is also given to compounds of formula 1 in which one of 1 and R2 represents a hydrogen atom and the other represents a hydroxy group.

Particularly preferred compounds provided by the present invention are (IH)-cis-1-((a-amino-2,316-drideoxy-α-L-lyxohexopyranosyl)oxy)-1,2,3 ,4,6,11-hexahydro-3,5
,12-)lihydroxy-6゜1i-dioxo-3-(
phenylcarbamoyloxy)methylnaphthacene, (IS)-cis-t-[(a-amino-2,3°6-drideoxy-α-L-arabinohexobyranosyl)oxy)-1,2,3,4,6 , 11-hexahydro3.
5.12-1lihydroxy=6.11-dioxo-3-
(Phenylcarbamoyloxy)methylnaphthacene, (l,5)-cis-1-[:(3-amino-2,3゜6
-drideoxy-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-3
,5,12-)lihydroxy-6゜11-dioxy-3
-(1(7?)-(phenylcarbamoyl)ethylfunaphthacene, (IS)-cis-1-[:(3-amino-2,3°6-
dorideoxy-α-L-arabinohexopyranosyl)oxy:]-]1.2,3,4,6.11-hexahydro3.5.12-trihydroxy-6,11-dioquine-
3-(1(R)-(phenylcarbamoyloxy)ethylfunaphthacene and a pharmaceutically acceptable acid addition salt thereof.

Examples of other interesting compounds provided by this invention are (IS)-cis-1-1m(3-amino-2,3°6-
dorideoxy-α-L-lyxohexinepyranosyl)oxy]-3-(4-chlorophenylcarbamoyloxy)
Methyl-1,2,3,4,6゜11-hexahydro-3
,5,12-)dihydroxy-6,11-dioxonaphthacene, (IS)-cis-1-[(3-amino-2,3
゜6-Drideoxy-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,5,12-)lihydroxy-3-(4-nitrophenylcarbamoyl) oxy)methyl-6,11-dioxonaphthacene, (IS)-cis-1-((3-amino-
2,3゜6-drideoxy-α-L-lyxohexinepyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,5,12-)lihydroxy-3-(4- Methoxyphenylcarbamoyloxy)methyl-6,11
-dioquinaphthacene, (IS)-cis-1,1:(3
-amino-2,3゜6-drideoxy-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,1
1-hexahydro-3,5,12-trihydroxy-3
-(3-hydroxyphenylcarbamoyloxy)methyl-6,11-dioquinaphthacene, (IS)-cis-
1-[(3-amino-2,3゜6-drideoxy-α-
L-lyxohexine pyranosyl)oxy)-1,2,3,
4,6,11-hexahydro-3,5,12-)lihydroxy-3-(methylcarbamoyloxy)methyl-6
, 11-dioxonaphthacene, (IS)-cis-t-[(a-amino-2,tortoise-6-drideoxy-α-L-lyxohexopyranosyl)oxy'
)-1,2,3,4,6,11-hexahydro-3,5
,12-)lihydroxy-3-<2-fenylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-cis-1-((3-amino-2,3°4.6
-titradeoxy-α-L-threohexopyranosyl)
(oxy)-1,2,3,4,6,11-hexahydro-
3,5,12-trihydroxy-6,11-dioxo-
3-(phenylcarbamoyloxy)methylnaphtase/
, (IS)-cis-1-((3-amino-2,3°4.6
-titradeoxy-α-L-threohexopyranosyl)
(oxy)-1,2,3,4,6,11-hexahydro-
3,5,12-trihydroxy-6,11-dioxo-
3-(3-pyridylcarbamoyloxy)methylnaphthacene, (IS)-cis-t-[(a-amino-2,3゜6-drideoxy-4-〇-methyl-α-L-lyquinhexopyranosyl) oxy)-3-(benzylcarbamoyloxy)methyl-1,2,3,4゜6.11-hexahydro-3,5,12-)lihydroxy-6,11-dioxonaphthacene, (IS)-cis- x-1: (a-amino-2,3゜6-drideoxy-α-L-lyxohexquinpyranosyl)oxy)-3-((2-carboxyethyl)carbamoyloxycomethyl-1,2,3, 4゜6
．． 11-hexahydro-3,5,12-)dihydroxy-6,11-dioquinaphthacene, (IS)-cis-1
-((3-amino-2,3゜6-drideoxy-α-L
-lyxohexopyranosyl)oxy)-1,2,3,4
,6,11-hexahydro-3,5,12-)lihydroxy-3-[:[2-(methoxycarbonyl)ethyl]
Carbamoyloxy]methyl-6,11-dioxonaphthacene, (IS)-cis-1-((a-amino-2,3°6-drideoxy-α-L-lyxohexopyranosyl)oxy)-1 ,2,3,4,6,11-hexahydro-3,5
,12-)lihydroxy-6゜11-dioxo-3-[
[2-(Propylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene, (IS)-cis-1-[3-amino-2,3°6-drideoxy-α-L-arabinohequinpyranosyl)oxy)-1, 2,3,4,6,11-hexahydro-3,5
,12-)lihydroxy-6,11-dioxo-3-[
[2-(Propylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene, (IS)-cis-1-((3-amino-2,3°6-drideoxy-4-0-methyl-α-L-11xo hexopyranosyl)oxy:]-1,2,3゜4.6.11-
hexahydro-3,5,12-trihydroxy-6,1
1-dioquine-3-(2-(phenylcarbamoyloxy)ethylfunaphthacene) and pharmaceutically acceptable acid addition salts thereof.

Further examples of compounds of interest provided by the present invention are (IS)-cis-t-[(a-amino-2,3°6-drideoxy-α-L-arabinohequinpyranosyl)oxy)-1,2, 3,4,6,11-hexahydro-3,
5,12-trihydroxy-6,11-dioxo-3-
(p-Tolylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-[(3-amino-2,3°6-drideoxy-4-0-methyl-α-L-lyxohexobyranosyl) oxy)-3-(carbamoyloxy)methyl-1,2,3,4,6,11-hexahydro-3,5
,12-)dihydroxy-6,11-dioxonaphthacene, (IS)-cis-1-((3-amino-2,3゜6-dolideoxy-4-0-methyl-α-L-lyxohexinpyra Nosyl)oxy]-1,2,3゜4.6.11-hexahydro-3,5,12-trihydroxy-6,11-
Dioquine-3-(phenylcarbamoyloxy)methylnaphthacene, (IS)-cis-t-((a-amino-2
,3゜6-drideoxy-4-0-methyl-α-L-lyxohexopyranosyl)oxy) -1,,2,3.

4.6.11-Hexahydro-3,5,12-trihydroxy-3-((o-nitrobenzylcarbamoyloxy)methyl)-6,11-dioxonaphthacene, naphthacene, (IS)-cis-x- ((a-amino-2,3°6-drideoxy-α-L-arabinohequinpyranosyl)oxy:]-]1.2,3,4,6.11-hexahydro3
．． 5.12-trihydroxy-a-(2-4enylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-cis-1-((3-amino-2,3°6-drydeoxy) α-L-arabinohequinpyranosyl)oxy)-t, 2. a, 4. e, tx-hexahydro-a,
s,12-)lihydroxy-a-(a-thenylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-cis-t-((a-amino-2,3゜6-drydeoxy-4- 0-Methyl-α-L-arabinohequinpyranosyl)oxy)-1+2,3゜4.6.11-hexahydro-3,5s12-)dihydroxy-6,11
-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-((3-amino-
2,316-drideoxy-4-0-ethyl-α-L-
lyxohexopyranosyl)oxy)-1,2,3゜4.
6.11-Hexahydro-3,5,12-trihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-((
a-amino-4-0-benzyl-2,3,6-drideoxy-α-L-liquinhequinpyranosyl)oxy)-'
+2+3.4,6.11-hexahydro-3,5,12
-trihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene 1 3.3ξ[tetramethylenebis(carbamoyloxymethylene)bis-(IS)-cis-[(3-amino-2,
3,4,6-titradeoxy-α-L-threohexopyranosyl)oxy]-1゜2.3,4,6.11-hexahydro-3,5゜12- ) IJ hydroxy-6,
11-Dioxonaphthacene, (IS)-cis-1-((a-amino-2,3°6-drideoxy-α-L-arabinohequinpyranosyl)oxy)-a-(4-chlorophenylcarbamoyloxy)
Methyl-1,2,3,4,6゜11-bexabidro 3
．． 5.12-1 Rehydroxy-6,11-dioxonaphthacene, (IS)-cis-x-((a-amino-2,3
+6-drideoxy-α-L-arabinohequinpyranosyl)oxy]-3-(carbamoyloxy)methyl-1
,2,3,4,6,11-hexahydro-3,5,12
-) dihydroxy-6,11-dioxonaphthacene, (IS)-cis-1-((3-amino-2,3°6-drideoxy-α-L-arabinohequinpyranosyl)oxy)-1,2, 3,4,6,11-hexahydro-a
, s, 12-trihydroxy-6,11-dioxo-3-(1(Sl(phenylcarbamoyloxy)
Ethylfunaphthacene, (IS)-cis-1-C(3-amino-2,3°6-drideoxy-4-0-methyl-α
-L-lyxohexopidinosyl)oxy]-1,2,3
゜4.6.11-hexahydro-3,5,12-trihydroxy-6,11-dioxy-3-[1(7?)-(
phenylcarbamoyloxy)ethylfunaftacene and their pharmaceutically acceptable acid addition salts.

According to the methods provided by the present invention, compounds of formula 1 and their pharmaceutically acceptable acid addition salts (α)R are hydrogen atoms, lower alkyl, aryl or aryl-(lower alkyl) groups, heteroatoms. is nitrogen, oxygen or sulfur, or a 5- or 6-membered heteroaromatic group of the formula (α
) or (b), in which R is a hydrogen atom, trichloroacetyl, lower alkyl, aryl or aryl-(lower alkyl) group, the heteroatom is oxygen or 5 which is sulfur
represents a group of formula (a) or a group of formula (a) above, and n' and X have the meanings given above;
However, all carboxy, hydroxy or amino groups present in the aryl substituent shall be in protected form, and the carboxy group present in the te group (α) shall be in protected form. In the formula, R3 represents an amino protecting group, n'1 and B I
each of 1 represents a hydrogen atom, or R11 and R
one of It represents a hydrogen atom and the other represents a lower alkoxy, benzyloxy or a reserved hydroxy group, and a force which cleaves one or more protecting groups present in the reaction product.・, (b) General formula In the formula, Ra, 7? II, R'' and represents a 5- or 6-membered heteroaromatic group or a group of formula (α) above, provided that any carboxy, hydroxy or amine groups present in the aryl substituent are in the protected form ""C, C,
and the isocyanate of the general formula % or the diisocyanate of the general formula %, in which nl has the above meaning, the carboxy group present in the group ((L) shall be in protected form) is reacted and the reaction product is In order to cleave one or more protecting groups present or to prepare a compound of formula 1 in which <C> R1 represents a lower akyoxy group, a compound of formula 1 in which R' represents a hydroxy group
and, if necessary, converting the compound of formula I into a pharmaceutically acceptable acid addition salt.

The carboxy or hydroxy group present at Rα in compound 2) can be protected in the form of a common easily hydrolyzable ester. Preferably, the ester group is derived from a lower alkane carboxylic acid such as acetic acid to protect the hydroxy group. The amine 7 group present in R can be protected using conventional methods, for example using a suitable acyl group.

The amino protecting group represented by Bs in compounds of formula H can be any amine protecting group commonly used in sugar chemistry. For example, Bs can represent a group such as chloroacetyl or trifluoroacetyl. If a protected hydroxy group is present in the compound of formula (1), this group can be a suitable protected hydroxy group known per se in sugar chemistry, for example p-nitrobenzoyloxy zero.

The reaction between the compound of formula (2) and the compound of formula m according to embodiment (α) of the present method can be carried out by a method known per se. In a preferred method, the reaction is carried out in an inert organic solvent and in the presence of a soluble salt.

Examples of inert organic solvents that can be used are sochloromethane, somethylalumamide, tetrahydrofuran, and the like. Preference is given to tetrahydrofuran and mixtures of tetrahydrofuran and dimethylformamide. For use in this reaction, it is advantageously carried out under atmospheric pressure.

The reaction of a compound of the formula m with a compound of the formula m produces a compound of the general formula 0 011 00HO where B(L, R'', R'', R'' and 'lJX have the above meaning f: no). , which is converted to the desired compound of formula ! by cleavage of the protecting group or groups present.

Cleavage of the protecting group or groups from the compound of the formula ■α can be carried out in a manner known per se. For example, if Ra represents a trichloroacetyl group, this group can be cleaved by treatment with an aqueous alkali, such as aqueous sodium hydroxide. For example, if R3 represents a trifluoroacetyl group, this group can still be cleaved by treatment with an aqueous alkali, such as aqueous thorium hydroxide. , R8 represents a chloroacetyl group, this group can be cleaved individually under neutral conditions using thiofrea. When one of R11 and R'' represents a p-nitrobenzoyloxy group, this group is
It can be converted to a hydroxyl group, for example by treatment with aqueous sodium hydroxide, or by appropriately choosing cleavage conditions, -
It will be clear that the process can be carried out in several steps.

The carboxy, droxy or amine 7 groups present in Rb in the incyanate of the formula 2α can be protected in a similar way to the formula PETA method already with regard to the protection of these groups of Ra in the compound of 2H.

The reaction of a compound of formula V with an isocyanate of formula Va or a soysodyne of formula Vb according to embodiment (b) of the process is advantageously carried out in a tertiary organic amine, such as for example virison. When using incyanates of the formula Vα, this reaction can advantageously be carried out at elevated temperatures, for example at temperatures from about 0°C to about 80°C. Isocyanate of formula ■ α is formula R
b-C0-N, and can be generated in situ by carrying out the reaction at a temperature at which the azide liberates nitrogen and rearranges to form the isocyanate. When using twin cyanates of the formula Vb, it is advantageous to carry out the reaction at about room temperature, suitably over an extended period of time.

In the general formula, R' is a trichloroacetyl, lower alkyl, aryl or aryl-(lower alkyl) group, the hetero atom is nitrogen, represents a 5- or 6-membered negative heteroaromatic group which is oxygen or sulfur, a group of the above formula (α) or a group of the formula 00HO; ", R", R", n' and The calgexyl group present in is a protected extension, resulting in a compound of which is converted to the desired compound of formula I by cleavage of one or more protecting groups.

Cleavage of the protecting group(s) from compounds of formula vb can be carried out analogously to the methods already described for the cleavage of one or more protecting groups from compounds of formula .alpha.

By esterification of a compound of formula I in which R' represents a hydroxy group with the embodiment of the process (6), the corresponding compound of formula I in which R1 represents lower alkoxy 4 can be produced in a manner known per se, e.g. can be carried out by treatment with a suitable noasialkane, such as soazomethane, or with a suitable lower alkanolic hydrogen chloride solution, such as methanolic hydrogen chloride.

Compounds of formula
sulfuric acid, phosphoric acid, etc.) and pharmaceutically acceptable organic acids (such as acetic acid, tartaric acid, citric acid, fumaric acid, maleic acid,
malic acid, methanesulfonic acid, toluene-4-monosulfo/acid, etc.) to form pharmaceutically acceptable acid addition salts.

The compounds of formula I contain two asymmetric carbon atoms in A-B of the aglycon moiety and therefore the present invention has within its scope (IS)-
It will be clear that both cis and (lR)-cis compounds are included.

The compound 2H used as a starting material in embodiment (α) of the method provided by the invention is a novel compound and also forms part of the invention.

For example, a compound of the general formula Ar wherein X has the above meaning and Ar represents an aryl group is a compound of the general formula The isocyanate of R (having any of the meanings of Z) is reacted with the diisocyanate of formula v6 above, and the reaction product of 1.3 - It can be produced by subjecting it to transesterification with nool and, if necessary, cleaving the trichloroacetyl group represented by Ra/ from the product.

Compound of formula (■) and isocyanate of formula (■) or formula VbI7
) The reaction with isocyanate is the reaction of compound 2 and formula V
It can be carried out analogously to the methods already described for the reaction with incyanates of a or soisocyanates of formula vb. Isocyanates of formula (1) can be prepared in situ from the corresponding azides in the manner already described.

The reaction product of formula (1) is then subjected to transesterification with 1,3-nol. This exchange is suitably carried out by reacting the compound of formula (1) with an excess of 1,3-sool in the presence of an acid. Particularly preferred 1.3-/ol is 2
-Methyl-2,4-pentanesol. Among the acids that can be used, lower alkanecarboxylic acids such as acetic acid are preferred.

This reaction is advantageously carried out in the presence of an oil-free organic solvent, such as a halogenated hydrocarbon such as dichloromethane, and at about room temperature.

Any cleavage of the trichloroacetyl group, represented by z/, from compounds of formula (1) can be carried out as already described for the cleavage of trichloroacetyl groups from compounds of formula (1) α.

The compound of formula (1) above can be produced, for example, as described in the Examples below or in a similar manner.

The compound of formula (2) used as the omega starter in embodiment (b) of the process provided by the invention is a novel compound and also forms part of the invention.

The compound of 2) is, for example, the general formula % formula %, where X has the above meaning, and R4 is a ryosyl group,
Preferably representing acetyl, is reacted with a compound of formula m above, and is prepared by deacylating the reaction product of the general formula, wherein R3, R4, R11XR11 and X have the meanings given above. can do.

The reaction of the compound of formula

Deacylation of compounds of 2XI can be carried out in conventional manner, for example by treatment with a suitable base.

The compound of formula X above can be prepared as described in the Examples below or analogously thereto.

The compounds of formula 1 and their agrochemically acceptable acid addition salts have antitumor activity.

The antitumor activity of the compound and its pharmaceutically acceptable acid addition salts is determined using standard pharmacological tests by dissolving the substance in water or, if insoluble, suspending it in propylene glycol. . Use solutions and suspensions for only 2 days,
Store in the dark at 4°C.

Mice were injected with 105 live lymphocytic leukemia tumor cells and received intraperitoneal (i.
Treatment was started with potato injection.

Untreated control animals died between 9 and 12 days.

The efficacy of treatment is expressed as the quotient T/C, which means the mean survival time of treated animals divided by the mean survival time of control animals IMJ. The results obtained in this test using representative compounds provided by the present invention are summarized in the following
Shown in the table: Table 1 Compounds: A: (IS)-cis-1-[(3-amino-2°3
．． 6-Dolideoxy-α-L-lyxo(sobilanosyl)oxy)-1,2,3,4°6.11-hexahydro-3,5,12-i-lyhydroxy-6,11-dioxo-3-ph tomoenylcarbamoyloxy)methylnaphthacene hydrochloride.

B: (IS)-cis-x-[+amyamino-.

3,6-)lysooxy-α-L-arabinohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-sooxo- 3-(Phenylcarbamoyl)methylnaphthacene hydrochloride.

C:fl)-cis-t-[(3-reminnow2,3.6-
Dorideoxy-α-L-lyxohexopyranosyl)oxy: l-1,2,3,4,6°11-power-1 major hydro-
3,5,12-)lihydroxy-3-(2-che3carpamoyloxy7)-methyl-6,11-sooxonaphthacene salt 1 D: (1,5)-cis-[( 3-Minnow 2.3.6
lotrideoxy-α-L-lyxohexopyranosyl)
oxy)-3-(4-chlorophenylcarbamoyloxy)methyl+1,2°3,4,6, . 11-hexahydro-3,5゜12-trihydroxy-6,11
- Sooxonaphthacene hydrochloride.

E: +l51-cis-1- ((3-amino-2゜3
．． 6-Drideoxy-4-〇-methyl-α-L-lyxohexopyranosyl)oxy]-3-(pentylcarbamoyloxy)methyl-1,2,3,4,6,11-hexahydro-3,5,12 -trihydroxy-6,11-
Sooxonaphthacene hydrochloride.

The compounds of formula I and their pharmaceutically acceptable acid addition salts can be used as medicaments, for example in the form of pharmaceutical preparations containing the compounds, in combination with compatible pharmaceutical carriers. can. The carrier material can be an inert organic or inorganic carrier material suitable for enteral (e.g. oral) or parenteral administration. Examples of such carrier materials are water, gelatin, talc, powder, stearic acid. Magnesium, arabic comb, 4i&!i oil, polyalkylene glycol, yellow petrolatum, etc.The pharmaceutical preparation can be manufactured in a conventional manner and the final dosage form can be a solid dosage form (e.g. tablets 11 can be liquid (e.g., liquidless, cloudy, milky lotion, etc.).Pharmaceutical preparations can be prepared by ordinary pharmaceutical operations. , for example, may be subjected to sterilization and/or may contain customary auxiliary agents, such as preservatives, stabilizers, wetting agents, buffers, salts for changing the osmotic pressure, etc. The pharmaceutical preparation Fj can also contain other therapeutically valuable substances.

The compounds of formula I and their pharmaceutically acceptable acid addition salts can be used as anti-tumor agents in continuous ingestion (eg, daily doses) or periodic ingestion (eg, monthly doses). Generally, the total dosage per treatment is approximately 25/
It will be in the range m' to 700/1/(m9 per square meter of skin area).

However, this dosing range is given as an example only and does not reflect the specific formula! It will be appreciated that the potency of the compound or salt can be increased or decreased depending on such factors as the potency of the compound or salt, the route of administration, and the severity of the condition being treated.

The following examples further illustrate the invention: Example 1 (a) (IS)- in tetrahydrofuran 100d
cis-1.2,3,4,6.11-hexahydro-1,
A solution of 1.3 g of 3,5,12-tetrahydroxy-6゜11-dioxo-3-(phenylcarbamoyloxy)methylnaphthane was cooled to -5°C and added with 2,3゜6-dioxo-3-dioxo-3-(phenylcarbamoyloxy)methylnaphthane in 1 Qsu of dichloromethane. Deoxy-4-O-1
)-Nitrobenzoyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride 1.3g
added.

The mixture was stirred while a solution of 0.652 g of silver trifluoromethanesulfone M in 15 d of diethyl ether was added over a period of 20 minutes. After the addition was complete, another 1.3 g of the above chlorosugar in 1 Q su of dichloromethane was added, then further 0.65 ml of silver trifluoromethanesulfonate in 15 ml of dry diethyl ether. li' was added over 20 minutes. The mixture was stirred at -5 DEG C. for 30 minutes, then poured into 100% potassium bicarbonate solution and extracted 4 times with 100% dichloromethane. The chloromethane extract was dried over anhydrous sodium sulfate and evaporated to give a red gum, which was columnarized on silica gel using hexane/ethyl acetate (1, vo 1/vo J) as eluent. Purified by chromatography.

After addition of 400 Iv of unreacted dioxonaphthacene starting material with dichloromethane/diethyl ether and crystallization, (lS)-cis-1-[(2,3,6-drideoxy-3-trifluoroacetamide-) was obtained in the form of red crystals. 4-0-p
-nitropenzoyl-α-L-lyxopyranosyl)oxy)-1,2,3゜4.6,11-hexahydro-3,
5,12-trihydroxy-6,11-dioxo-3-
(Phenylcarbamoyloxy)methylnaphthacene1.
16 jj were obtained.

(b) 1.7 g of the compound obtained according to section (a) was dissolved in a mixture of 100d dichloromethane and 1001d methanol and the resulting solution was OCR cooled. 0.1M
Aqueous sodium hydroxide solution was added to turn the mixture brown-purple, and the mixture was stirred at 0°C for 1.5 hours. The reaction was stopped by the addition of acetic acid to restore the orange color, the mixture was diluted with 250 ml of water and extracted 4 times with 100 ml each of dichloromethane. The combined dichloromethane extracts were dried over anhydrous sodium sulfate and evaporated to a small volume. Addition of diethyl ether prevents swirling, (IS)-cis-
1”-[(2,'3.6-)lysooxy-3-trinoroacetamide α-L-lyxohexopyranosyl)
oxo)-1,2,3,4,6,11-hexahydro-
3,5,12-trihydroxy-6,11-dioquine-
This results in the precipitation of 3-(phenylcarbamoylmexy)methylnaphthacene, which has a melting point of 160-170 after FM.
Obtained as an orange powder at ℃; [α17=+x36.9°
(c=0.1% in chloroform).

A solution of 680 mg of the compound obtained according to (cl Section (bl) in tetrahydrofuran 10- was ice-cooled 0,1
Added to 60ml of M sthorium hydroxide solution. Mixture at 0℃
The mixture was stirred at room temperature for 45 minutes and then at room temperature for 30 minutes.

The solution was adjusted to a pH value of 8-9 by addition of 0.1 M hydrochloric acid and then extracted repeatedly with dichloromethane containing 10% ethanol until the extract was practically colorless. The combined extracts were washed with water, dried over anhydrous sodium sulfate, and evaporated to give a red gum. This gum was dissolved in 15 m of dichloromethane containing 3+/m of methanol and filtered. 4 mg of 0.25M methanolic hydrogen chloride was added followed by 250 Wit of dry diethyl ether with swirling.

The precipitated product was collected by filtration, washed with dry diethyl ether and dried under vacuum, mp 175-177.
(IS)--cis-1 in the form of an orange-red powder at °C (decomposed).
-[(3-amino-2,3゜6-drideoxy-α-L
-lyxohexopyranosyl)oxy]-1, 2, 3, 4
, 0.549 of 11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene hydrochloride was obtained;
α) v=+158.9° (c=0.05% in methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-1,3, used as starting material in section (a)
5,12-tetrahydroxy-6,11-dioxo-3
-(Phenylcarbamoyloxy)methylnaphthacene was prepared as follows: yama (IS)-cis-1,2,
3,4,6゜11-hexahydro-5+12-dihydroxy-3-hydroxymethyl-6,11-dioxo-1
, 0.8 g of 3-naphthacenediylbenzene boronate was dissolved in pyridine 100-, and phenylisonanate 0.
．． Added 9g. The mixture was heated to 60° C. for 45 minutes, cooled and the solvent was removed by evaporation. The residue was taken up in 100 ml of dichloromethane, the colorless insoluble material was separated, the filtrate was added with 5 Q ml of 5M hydrochloric acid, and 50 ml of sphagnum moss was added.
-l twice, dried over anhydrous sodium sulphate and evaporated to give the crude (IS)-cis-1,2, as a red solid.
3,4゜6.11-hexahydro-5,12-dihydroxy-6,11-dioxo-3-(phenylcal)(
Moyloxy)methyl-1,3-naphthacenediylbenzene boronate was obtained, which was used without further purification.

(11) The benzene boronate obtained according to clause (1) was dissolved in dichloromethane 30117% 2-methyl-2,4-
Dissolved in a mixture of pentanediol 3Qid and acetic acid 3d, and the solution was left at room temperature overnight. The solution was diluted with 100 ml of dichloromethane, washed three times with 100 tnl of wood, dried over anhydrous sodium sulfate and evaporated. The residue was triturated with ethyl acetate/diethyl ether to give (IS)-cis-1,2,3,4°6.11-hexahydro-1,3 in the form of red crystals with a melting point of 225-226°C.
,5,12-tetrahydroxy-6,11-dioquine-
3-(phenylcarbamoyloxy)methylnaphthacene 0, Pi 2.9 was obtained; [α'l”=+136.0
° (c=o, coefficient 05, in dioxane).

(IS)-cis-1,2,3,4,6,11-hexahydro-5,12 used as starting material in section (1)
-Dihydroxy-3-hydroxymethyl-6,11-dioxo-1,3-naphthacenediylbenzeneboronate was prepared according to the method described below or (B): (A) (Is)-cis-3- Acetoxymethyl-1,2
,3,4,6,11-hexahydro-1゜3.5.12
-tetrahydroxy-6,11-dioxonaphthacene 2
．． 0 g to 250 d of dichloromethane and 25 d of methanol
Dissolved in the mixture of 0d.

The mixture was stirred at room temperature and a sufficient amount of 0.1 M
An aqueous solution of IJ (hydroxide) was added to maintain the deep purple color. The mixture was stirred for 5 hours. The reaction was quenched by the addition of acetic acid, the color returned to orange, and most of the solvent was removed by evaporation. 100 d of water was added to the residue and the resulting orange-red precipitate was collected by filtration and dried under vacuum. (IS)-cis- in the form of orange-red crystals with a melting point of 212-214°C
1,2゜3.4,6,11-hexahydro-1,3,,
5゜12-nato2hydroxy-3-hydroxymethyl-
6,11-dioxonaphthacene 1.7/1 obtained: [:L)7=+131.3°(c=0.1
%, Geo #”j on).

4.0 g of the compound obtained according to the above section was added to 1000100 O of tetrahydrofuran! Make it cloudy, add benzeneporonic acid 2
．． 5, i17 and 0.1 g of acetic acid. The mixture was heated under reflux for 30 minutes, cooled and the solvent was removed by evaporation to give a red residue. After disintegration with methanol, it appears as an orange-red crystal with a melting point of 258-259°C (IS).
-cis-1,2,3,4゜6.11-hexahydro-5
,12-dihydroxy-3-hydroxymethyl-6,1
4.65 g of 1-dioxo-1,3-naphthacenediylbenzene boronate were obtained; [α]2D. =+'35
5.0' (c=0.1, dioxane).

(B) (Is)-cis-3-acetoxymethyl-1,2
, 3,4,6,11-hexahydro-5゜12-dihydroxy-6,11-dioxo-1゜3-naphthacenediylbenzene boronate i, o, p in dichloromethane 10
〇- and 100 d of methanol. The mixture was stirred at room temperature and sufficient aqueous 0.1 M hydroxide solution was added to turn the color deep purple.The C5 mixture was stirred for 4 hours and then quenched by the addition of acetic acid to turn orange. I returned it. The solvent was removed by evaporation and the residue was triturated with methanol to give an orange-red crystalline form (IS
)-cis-1,2,3,4,6,11-hexahydro-
5,12-dihydroxy-3-hydroxymethyl-6,
11-Dioxo-1,3-naphthacenediylbenzene boronate (1.7 g)
It was identical to the compound prepared according to.

Example 2 (a) (IS)-cis-3-(4-chlorophenylcarbamoyloxy)methyl-1,2,3, in tetrahydrofuran 200d and dimethylformamide 141,
2.0 g of 4,6,11-hexahydro-1,3,5,12-tetrahydroxy-6,11-thioxonaphthacene
The solution was cooled to -5°C and dichloromethane 2011j
The 2.3.6-doriteoxy-4-0-p-nitrobenzoy in the solution was treated with 2.0 g of -3-trifluoroacetamide-α-L-lyxohexine pyranosyl chloride. Then silver trifluoromethanesulfonate in 2511/1. dry diethyl ether. Og was added dropwise over 20 minutes. After the addition was complete, chlorosugars 2.0.9 and 1.0.9 and trifluoromethanesulfonic acid 1.9 were added under similar conditions, respectively. Two further additions were made using OI and 0.5 g. The mixture was then stirred at -5°C for 30 minutes and 10%
The mixture was poured into 400 d of potassium hydrogen carbonate solution and extracted four times with 200 ml of dichloromethane each.

The dichloromethane extract was dried over anhydrous sodium sulfate and evaporated to give a red gum, which was purified on silica gel with acetone/dichloromethane (1:5) as eluent.
, vol/vol) and purified by column chromatography. In addition to 575 η of unreacted dioxo-7tacene starting material, (IS)-cis-3-(4-chlorophenylcarbamoyloxy)methyl-1-((2,3, 6-drideoxy-3-trifluoroacetamide-4-〇-p
-Nitrobenzoyl-α-L-lyxohexopyranosyl)oxy:)-1,2,3,4,6,11-hexahydro-3,5,12-)dihydroxy-6,11-dioxonaphthacene 1.51.9 was obtained; [α]^=-6
0.1° (c=0.05% in dioxane).

(b) Compounds obtained according to section (a) in Example 1
(IS)-cis-3-(4-chlorophenylcarbamoyloxy)methyl-1-((2,3,6-trideoxy-3-trifluoro Acetamide-α-L-lyxohexopyranosyl)oxy) -1゜2.3,4,6,11
-hexahydro-3,5゜12-trihydroxy-6,
11-Dioxonaphthacene was obtained, which was used without further purification.

(C) Compound obtained according to section (b) in Example 1
(C), melting point 177-17
(IS)-cis-1-[(3-
Amino-2,'3,6-drideoxy-α-L-lyxohexopyranosyl)oxy)-3-(4-chlorophenylcarbamoyloxy)-methyl-1,2,3,4,6
, 11-hexahydro-3゜5.12-)dihydroxy-6,11-dioxonaphthacene hydrochloride was obtained;
α)”=+159.9° (c=0.05% in methanol).

(is)-cis-3-(4-chlorophenylcarbamoyloxy)methyl-1,2,3,4,6,11-hexahyto0-1.3 used as starting material in section (a)
,5.12-tetrahydroxy-6,11-dioxonaphthacene could be prepared as follows: Following the method described in Example 1, (1s)-cis-
1,2,3,4,6,11-hexahydro-5,12-
Dihydroxy-3-hydroxymethyl-6,11-dioxo-1,3-naphthacenediylbenzeneboronate 1
．． 0.9 of 4-chlorophenylisocyanate in 100-J of pyridine,! 9 was reacted. In the same manner, (IS)-cis-3-(4-chlorophenylcarbamoyloxy)methyl-1,2,3,
4,6°11-hexahydro-5,12-dihydroxy-6,11-dioxo-1,3-naphthacenediylbenzene boronate was obtained and was used without further purification.

(11) The benzene boronate obtained according to clause (1) was treated according to the method described in Example 1(ii) to form (IS)-cis-
3-(4-chlorophenylcarbamoyloxy)methyl-1,2,3,4,6,11-hexahydro-1,3,
5,12-tetrahydroxy-6,11-dioxonaphthacene was obtained: [α)V=+12 s, 1°(
c = 0.05% in dioxane).

Example 3 (a) Following the method described in Example 2(a), (IS
)-cis-1,2,3,4,6,11-hexahydro-
162 g of 1,3,5,12-tetrahydroxy-3-(4-nitrophenylcarbamoyloxy)methyl-6,11-dioxonaphthacene was dissolved in 2°3.6-)lysooxy-4-0-p-nitrobenzoyl. -3-Trifluoroacetamide-α-trilyxohexopyranosyl chloride.

After chromatography, in addition to the unreacted dioxonaphthacene starting material 254~, mp 208-210
(IS)-cis-1-((2,3
, 6-drideoxy-3-trifluoroacetamide-
4-0-p-nitrobenzoyl-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-3-(4
-nitrophenyl(rubamoyloxy)-methyl-6,
959■ of 11-dioxonaphthacene was obtained; [α)
”=-60.1° (c=0.05° in dioxane).

(b) Compound obtained according to section fa) in Example 1
(IS)-cis-1-(:(2,3,6-)lysooxy-3-fluoroacetamide-α-L-lyxohexinepyrano sil)oxy)-1,2,3,4゜6.11-hexahydro-3,5,12-)dihydroxy-3-(4-
Nitrophenylcarbamoyloxy)methyl-6,11
-dioxonaphthacene was obtained, which was used without further purification.

(c) Compound obtained according to section (b) in Example 1
Processed according to the method described in (C), melting point 175-17
(IS)-cis-1- in the form of an orange-red powder at 8°C (decomposed).
C(3-amino-2,3,6-)lysooxy-α-L-
lyxohexine pyranosyl)oxy]=1.2,3,4,
6.11-hexahydro-3゜5.12-)lysooxy-3-(4-nitrophenylcarbamoyloxy)methyl-6# 11-dioxonaphthacene hydrochloride was obtained; [α]20=-151 , 8° (c=0.05% in methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-1,3, used as starting material in section (a)
5,12-tetrahydroxy-3-(4-nitrophenylcarbamoyloxy)methyl-6#11-dioxonaphthacene was prepared as follows: (1) (IS)-cis-1 in 100d of pyridine. ，
1.0
．． A solution of 1.0 I of 9 and 4-nitrobenzoyl azide was heated to 75° C. for 1.25 hours, cooled, and then the pyridine was removed by evaporation.

The red residue was poured into 200ml of dichloromethane, the insoluble material was filtered out, the solution was poured into 50ml of 5M hydrochloric acid, and 1 ml of sphagnum moss was added.
Washed twice at 00m. After drying over anhydrous sodium sulfate, the crude (IS)-cis-1,2,3 was red and rubbery.
, 4,6,11-hexahydro-5,12-dihydroxy-3-(4-nitrophenylcarbamoyloxy)methyl-6,11-dioxo-1,3-naphthacenediylbenzene boronate was obtained. was used without further purification.

The benzene boronate obtained according to paragraph (11) (:) was treated according to the method described in Example 1 (it).

(Is) - in the form of orange-red crystals with a melting point of 237-239°C
cis-1,2,3,4,6,11-hexahydro-1,
3,5,12-tetrahydroxy-3-(4-nitrophenylcarbamoyloxy)methyl-6,11-dioxonaphthacene was obtained; C(%'=+117.4
° (c = 0.05% in dioxane).

Example 4 (a) Following the method described in Example 1(a), (IS
)-cis-1.2.3,4,6.11-hexahydro-
1,3,5,12-tetrahydroxy-3-(4-methoxyphenylcarbamoyloxy)methyl-6,11-
1.0 g of dioxonaphthacene was reacted with 2°3.6-drideoxy-4-0-p-nitropenzoyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride. After chromatography, in addition to the unreacted dioxonaphthacene starting material 60~, (IS)-cis-1-((2,3,6-1 Lysooxy-3-trifluoroacetamide-4-0-1)-nitrobenzoyl α
-L-lyxohexopyranosyl)oxy]-1,2,3
,4,6,11-hexahydro-3,5,12-)dihydroxy-3-(4-methoxyphenylcarbamoyloxy)methyl-6,11-dioxonaphthacene 897q
was obtained; [α)','=-69.1° (c=0.0
5 Ch. in dioxane).

(b) Compounds obtained according to section (a) in Example 1
(b) in the form of orange crystals (I
S)-cis-1-[2,3,6-)lysooxy-3-trifluoroacetamide-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6゜11-hexahydro -3,5,12-)dihydroxy-3-(4-methoxyphenylcarbamoyloxy)methyl-6,11-
Dioxonaphthacene was obtained and was used without further purification.

(c) Compound obtained according to section (b) in Example 1
(C), melting point 183-18
(IS)-cis-1- in the form of an orange-red powder at 5°C (decomposed).
((3-amino-2,3,6-drideoxy-α-L-
lyxohexopyranosyl)oxy]-1,2,3,4,
6,11-hexahydro-3゜5.12-)dihydroxy-3-(4-methoxyphenylcarbamoyloxy)
Methyl-6,11-dioxonaphthacene hydrochloride was obtained; [α]20=+152.9° (c=0.05% in methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-1,3, used as starting material in section (a)
5,12-Tetrahydroxy-3-(4-meth)xyphenylcarbamoyloxy)meth-6.11-dioxonaphthane was prepared as follows.

(1) According to the method described in Example 3, (IS)-cis-1,2,3,4,6,11-hexahydro-5,12
-dihydroxy-3-hydroxymethyl-6,11-dioxo-1,3-naphthacenediylbenzeneboronate 0.7I in pyridine 4-methoxybenzoyl azide 2. Reacted with Oj9 to form (1s)-cis- in the form of a red rubber.
1,2,3,4゜6.11-hexahydro-5,12-
Dihydroxy-3-(4-me)xyphenylcarbamoyloxy)methyl-6,11-dioxo-1,3-naphthacenediylbenzene boronate was obtained and was used without further purification.

The benzene poronate obtained according to section (+) was treated according to the method described in Example 1 (++).

(IS)-cis-1,2,3,4,6,11-hexahydro-1,3 in the form of orange-red crystals with a melting point of 196-197°C
, 5,12-tetrahydroxy-3-(4-methoxyphenylcarbamoyloxy)methyl-6,11-dioxonaphthacene 675 my; [α] Sweet + 156.6
° (c = 0.05 h in dioxane).

Example 5 (a) Following the method described in Example 1(a), (1s
)-cis-3-(3-acetoxyphenylcarbamoyloxy)methyl-1,2,3,4,6,11-hexahydro-1,3,5,12-tetrahydroxy-6,11
- 1.4 p of dioxonaphthacene was treated with 2.3.6-drideoxy-4-0-p-nitrobenzoyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride. After chromatography, in addition to the unreacted dioquinaphthacene starting material 191
(IS)-cis-3-(acetoxyphenylcarbamoyloxy)methyl-1-((2,3,6-)lysooxy-3-trifluoroacetamide-4-〇 in the form of orange-red crystals with a melting point of 175-177°C -p-nitrobenzoyl-α-L-lyxohexobin2-nosyl)oxy]-1,2,
3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxonaphthacene 80619
was obtained; [α]', 7=-62,8° (c=0.0
5% in dioxane).

(b) 1 m Compound 0.9 obtained according to (a)
5 g dichloromethane 100 and methanol 100
- dissolved in a mixture of A 0.1M aqueous sodium hydroxide solution was added to make the color deep purple, and the solution was stirred at room temperature for 3.5 hours. Add acetic acid to return the color to orange, and add 250 ml of water to the mixture.
d and the solution was diluted with 100 ml of dichloromethane 4 times
Extracted twice. The bottom dichloromethane extract was dried over anhydrous sodium sulfate and evaporated to obtain a red gum. Disintegrate with diethyl ether to form (IS)-
cis-1-[(2,3,6-)lysooxy-3-trifluoroacetamido-α-L-lyxohexopyranosyl)oxy: l-1,2,3,4,6,11-hexahydro- 710 wIg of 3,5,12-trihydro-3-(3-hydroxyphenylcarbamoyloxy)-methyl-6,11-dioxonaphthacene was obtained.

(C) Compound 690# obtained according to section (b) was treated according to the method described in Example 1(C) to give a melting point of 17
(Is)-cis-1-((3-amino-2,3,6-drideoxy-α-L-liquinhequinpyranosyl)oxy]-1 in the form of an orange-red powder at 8 to 180°C (decomposition) ,2,
3,4,6,11-hexahydro-3,5,12-trihydroxy-3-(3-hydroxyphenylcarbamoyloxy)methyl-6,11-dioxonaphthacene hydrochloride 575 was obtained; [α ] Amase+135.5° (c=0
．． 05 in methanol).

(IS)-cis-3-(3-acetoxyphenylcarbamoyloxy) used as starting material in section (a)
Methyl-1,2,3,4,6,11-hexahydro-1
,3,5,12-tetrahydroxy-6,11-dioquine naphthacene was prepared as follows: (1) (IS)-ns 1,2 in pyridine;
3゜4.6.11-hexahydro-5,12-dihydroxy-3-hydroxymethyl-6,11-dioquine-1
,3-naphthacenediylbenzenepolone) 0.69
and 0.6 g of 3-acetoxybenzoyl azide was heated to 80° C. for 35 minutes, and then an additional 0.7.9 g of 3-acetoxybenzoyl azide was added. Heat for another 45 minutes
The solvent was removed by evaporation, the residue was taken up in 200 d of dichloromethane, and the insoluble material was filtered out. F
The solution was washed twice with 50 l of 5M hydrochloric acid and 50 l of water, dried over anhydrous sodium sulfate and evaporated to give an orange-red rubbery crude (IS)-cis-3-(3-acetoxyphenylcarbamoyloxy). ) Methyl-1,2,3,
4,6,11-hexahydro-5.12-dihydroxy-6,11-dioquine-1.3.-7tacenediylpenzene poronate was obtained and was used without further purification.

(11) The benzene boronate obtained according to clause (1) was treated according to the method described in Example 1 (++1).

Red rubbery (IS)-cis-3-(3-acetoxyphenylcarbamoyloxy)methyl=1,2°3.4.
6.11-hexahydro-1,3,5゜12-tetrahydroxy-6,11-dioxonaphthacene 0.71/l
was obtained and used without further purification.

Example 6 (a) Following the method described in Example 1(a), (IS
)-cis-1,2,3,4,6,11-hexahydro-
1.1 g of 1,3,5,12-tetrahydroxy-3-(methylcarbamoyloxy)methyl-6,1-edioxonaphthacene to 2.3.6-)lysooxy-4-0-1
)-nitropenzoyl-3-trifluoroacetamide-α-L-liquinhequin pyranosyl chloride. After applying chromatogelane, red rubber-like (I
S)-cis-1-((2,3,6-)lysooxy-3-
trifluoroacetamido-4-0-1)-nitrobenzoyl-α-L-lyxohexopyranosyl)oxy]-
1,2,3,4,6,11-hexahydro-3,5,1
2-4lihydroxy-3-(methylcarbamoyloxy)methyl-6,11-dioxonaphthacene was obtained, which was used without further purification.

Example 1 Compounds obtained according to Section bl (al)
(b) in the form of an orange powder (I
S)-cis-1-[(2,3,6-)lysooxy-3-
Trifluoroacetamido-α-L-lyxohexopyranosyl)oxy:]-1,2,3,4゜6.11-hexahytol:I-3,5,12-)dihydroxy-3-(
Methylcarbamoyloxy)methyl-6,11-dioxophtacene was obtained, which was used without further purification.

Compounds 650~ obtained according to section cl (bl) were treated according to the method described in Example 1(C), melting point 17
(IS)-cis-1-((3-amino-2,3,6-)lysooxy-
α-L-lyxohexopyranosyl)oxo)-1,2,
3,4,6,11-hexahydro-3,5,12-)dihydroxy-3-(methylcarbamoyloxy)methyl-6,11-dioxonaphthacene sulfate was obtained; [α]
20 = +143.8° (c = 0.05 cm, methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-1,3, used as starting material in section (a)
5,12-tetrahydroxy-3-(methylcarbamoyloxy)methyl-6,11-dioxonaphthacene was produced as follows = (1) Pi')')7100R
+7 in 1) (Is)-1,2°3.4,6.11-hexahydro-5,12-dihydroxy-3-hydroxymethyl-6,11-dioxo-1,3-naphthacenediylbenzeneboronate A mixture of 1.0 g and 2.5 g of methyl incyanate was heated to 70° C. for 3 hours. The solvent was removed by evaporation, the residue was dissolved in dichloromethane and the solution was washed twice with 5M hydrochloric acid 5Q*/ and with 50ml of sphagnum moss. The solution was dried over anhydrous sulfuric acid and evaporated to give a red gummy crude (1s)-cis-1,
2,3,4,6,11-hexahydro-5+ 12-dihydroxy-3-(methylcarbamoyloxy)methyl-6,11-dioxo-1,3-naphthacenediylbenzene boronate was obtained, which was further purified. It was used without purification.

(i) Treating the benzene poronate obtained according to section (1) according to the method described in Example 1 (il),
In the form of orange-red crystals with a melting point of 216-218°C (IS)
-cis-1,2,3,4,6,11-hexahydro-
1,3,5,12-tetrahydroxy-3-(methylcarbamoyloxy)methyl-6,11-dioxonaphthacene was obtained; [α:]”=+130° (c=0.05
(in charge, dioxane).

Example 7 (al) Following the method described in Example 1(a), (IS
)-cis-1,2,3,4,6,11-hexahydro-
0.9 g of 1,3,5,12-tetrahydroxy-3-(2-thenylcarbamoyloxy)methyl-6゜11-dioxonaphthacene was converted into 2,3,6-trithioxy-
4-0-p-Nitrobenzoyl-3-trifluoroacetamide-α-L-lyxohexine pyranosyl chloride was treated twice with 1.81 each. After chromatography K, in addition to the unreacted dioxonaphthacene starting material 80~, orange-red crystals (IS
)-cis-1-[(2,3,6-drideoxy-3-trifluoroacetamido-4-0-p-nitrobenzoyl-α-L-lyxohexopyranosyl)oxy]-1,
2,3,4,6,11-hexahydro-3,5,12-
) dihydroxy-3-(2-thenylcarbamoyloxy)methyl-6,11-dioquinaphthacene 800m9
was gotten.

(b) Compounds obtained according to Section (al) in Example 1
(b), melting point 154-15
(IS)-cis-1-((2°3.
6-drideoxy-3-trifluoroacetamide-α
-L-lyxohexopyranosyl)oxy:]-]1.2
,3,4,6.11-hexahydro3.5.12-trihydroxy-3-(2-thenylcarbamoyloxy)
Methyl-6,11-dioxonaphthacene was obtained; [α]
”=+142.3° (c=0.05°, in dioxane)
.

(c) Compound obtained according to section (b) in Example 1
(c), melting point 178-18
(IS)-cis-1-[(3-amino-
2,3,6-)lysooxy-α-L-lyxohexopyranosyl)oxy]-1,2,3,4゜6-1 i-hexahydro-3,5,12-)dihydroxy-3-( 2-
chenylcarbamoyloxy)methyl-6,11-dioxonaphthacene hydrochloride was obtained; [α:]7=+xza,
g° (c=0.05% in methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-1°3. used as starting material in section (al).
5.12-Tetrahydroxy-3-(2-thenylcarbamoyloxy)methyl-6*11-dioxonaphthacene was produced as follows.

(1) (IS)-cis-1゜2.3,4,6,11-hexahydro-5,12-dihydroxy-3-hydroxymethyl-6,11-dioxo-1,3-natsuta in pyridine 100- Sendiylbenzene boronate 1. (
A solution of 3.09 g of thiophene-2-carboxylic acid azide and thiophene-2-carboxylic acid azide was heated to 75° C. for 1.5 h, cooled, and heated for an additional 1.5 h at room temperature.
It was left for 6 hours. The pyridine was removed by evaporation and the red residue was taken up in 200 ml of dichloromethane. Insoluble material was filtered out and the solution was washed twice with 50 dl of 5M hydrochloric acid and 100 ml of sphagnum moss. After drying over anhydrous sodium borate, the solvent was removed by evaporation and the residue was purified by chromatography on silica gel using ethyl acetate/n-hexane as eluent. death,
(IS)-cis-1,2,3°4.6.11 in the form of orange-red crystals with a melting point of 243-245°C (crystals from ethyl acetate)
-hexahydro-5,12-dihydroxy-3-(2-
chenylcarbamoyloxy)methyl-6,11-dioxo-1,3-naphthacenediylbenzeneborone) 1
．． 035g was obtained; [α)”=+271.5°(c=
0.05% in dioxane).

(Ii) The benzene boronate obtained according to section (1) was treated according to the method described in Example 11i) to give (IS)-cis-1,2,3 in the form of an amorphous orange powder with a melting point of 144-146°C. ,4,6,11-hexahydro-1,3
, 5,12-tetrahydroxy-3-(2-thenylcarbamoyloxy)methyl-6°11-dioxonaphthacene was obtained.

Example 8 (a) (IS)-cis-1,2,3,4,6.11-hexahydro-1,3, in tetrahydrofuran 100-
5,12-tetrahydroxy-6゜11-dioxo-3
+ A solution of 1.5I (phenylcarbamoyloxy)methylnaphthacene was cooled to -5°C, and dichloro12
2,3゜6-dorideoxy-4-0-p in 739 ml
-Nitrobenzoyl-3-trifluoroacetamide-
Xopyranosyl chloride 2,5 was added to α-L-arabino.

The mixture was stirred while 1.25 ml of silver trifluoromethanesulfonate in dry diethyl ether was added. i solution at 30
Added over a period of minutes. After the addition is complete, dichloro77
1.0 I of the above chlorosugar in 715 ml was added followed by 511 Is of trifluoromethanesulfonic acid fao in 15 d of dry diethyl ether over a period of minutes. The mixture was stirred for 30 minutes at -5°C, then poured into 500 ml of 10% potassium bicarbonate solution and dichloromethane 1 ml each.
Extracted 4 times at 50 m. The dichloromethane extract was dried over anhydrous sodium sulfate and evaporated to give a red gum, which was purified by crystallization from dichloromethane. (IS)-cis-1-C(2,3,6-)lysooxy-3-trifluoroacetamido-4-〇-p-nitrobenzoyl-alpha in the form of red crystals with a melting point of 270-272°C.
-L-arabinohexopyranosyl)oxy]-1,2,
3,4,6゜11-hexahydro-3,5,12-)lihydro*" 6 p 11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene 1.016,
Obtained 9; [α] Sweet +262.9° (c=o, '05
H, in dioxane). The mother liquor from the above crystallization was purified on silica gel with the eluent being ethyl acetate/hexane (1:1).
) to give the same product, 0.16, li', and unreacted dioxonaphthacene starting material, 0.18, F.

(b) 1.05 g of the compound obtained according to clause (a)
was treated according to the method described in Example 1(b) and had a melting point of 2
(IS)-cis-1- in the form of orange crystals at 24°C.
(2,3,6-drideoxy-3-trifluoroacetamido-α-L-arabinohequinpyranosyl)oxy]
-1,2,3,4,6,11-hexahydro-3,5,
12-trihydroxy-6゜11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene 0.79
g; [α]20=+186.0° (cz0.0
49 in dioxane).

(cl Compound 0.68 obtained according to clause (b)
fI was processed according to the method described in Example 1(c) to give an orange-red powder (is
)-cis-1-[(3-amino-2,3,6-1-lysooxy-α-L-arabinohequinpyranosyl)oxy]
-1,2,3,4,6,11-hexahydro-3,5,
12-) Dihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene hydrochloride 0
．． Got 59.9: [α]! O=+206.6°(cz
0°05cm in methanol).

Example 9 (a) Following the method described in Example 1(a), (1s
)-cis-1,2,3,4,6,11-hexahydro-
1,3,5,12-tetrahydroxy-6゜11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene 1.37.9 to 2.3,4゜6-tetradeoxy-3-trifluoroacetamide- It was treated with 1.75 g of α-L-threohexopyranosyl chloride and 1.25 g of silver tolynefluoromethanesulfonate. After chromatography on silica gel using dichloro, methane containing 5% acetone as eluent, unreacted dioxonaphthacene starting material 462~ plus m.p. 155~
(IS)-cis-1-[(2
, 3,4,6-tetradeoxy-3-trifluoroacetamido-α-L-threohexopyranosyl)oxy]
-1,2,3,4,6゜11-hexahydro-3,5,
12-) Dihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene 5851
Obtain W; (cz)y=+1 s 4.6°(cz
0.05% in dioxane).

(b) Compound 0.609 obtained according to clause (a)
was dissolved in tetrahydrofuran 2011/2011, and this solution was added to an ice-cooled 0.1 M aqueous sodium hydroxide solution. The mixture was stirred at 0°C for 3 hours, then the solution Op.
The H value was adjusted to 8-9 by addition of 0.1M hydrochloric acid.

This solution was repeatedly extracted with dichloromethane containing 10 parts of ethanol until the extract was practically colorless. The combined extracts were washed with water, dried over anhydrous sodium sulfate, and evaporated to give a red gum. This gum was dissolved in 20 d of dichloromethane, filtered and 4 d of 0.25M methanolic hydrogen chloride were added. While swirling, 200 d of dry diethyl ether was added to obtain a product in the form of an orange precipitate. After filtering and drying under vacuum, melting point 17
(IS)-cis-1-[(3-amino-2°3.4.6-titradeoxy-α-L-threohexopyranosyl)oxy] in the form of an orange-red powder at 3-175°C (decomposed). -1
,2,3,4,6゜11・-hexahydro-3,5,1
2-trihydroxy-6111-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene hydrochloride 144
Obtained 0■; [α]”=+205.1° (cz0.0
5% in methanol).

Example 10 (a) (Is)-cis-1-[(2,3,4,6-tetradeoxy-3-trifluoroacetamide-α-L-
threhexopyranosyl)oxy]-1,2,3,4,
6,11-hexahydro-3°5.12-)dihydroxy-3-hydroxymethy#-6,11-dioxonaphthacene 5o1n9 was dissolved in 75m of dry viridi, and 100~ of phenyl isocyanate was added. Mixture to 700 to 3
Heat for 0 min, cool and remove solvent by evaporation.

The residue was taken in dichloromethane 30a+jK, some of the insoluble substances were removed, and the p solution was purified by chromatogelane and (1s)-cis-1-C(2,3゜4.6-tetradeoxy-3-trifluoro Acetamide-α-L
-threohexopyranosyl)oxy]-1,2,3,4
,6,11-hexahydro-3,5,12-)dihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene 52~, which was obtained according to Example 9(a) It was the same as the compound obtained.

(b) The compound obtained according to Section (al) in Example 9
(1s)-cis-1-C(3-amino-2,3,4,6-titradeoxy-α-L-threohexopyranosyl)oxy, )−
1,2,3,4,6,11-hexahydro-3,5,1
2-) Dihydroxy-6,11-dioquine-3-(phenylcarbamoyloxy)methylnaphthacene hydrochloride was obtained, which was identical to the compound obtained according to Example 9(b).

(IS)-cis-1-[(2,3,4,6-tetradeoxy-3-)! was used as the starting material in section (a).
J fluoroacetamido α-L-threohexopyranosyl)oxy]-1,2,3,4゜6.
11-hexahydro-3,5,12-)dihydroxy-
3-Hydroxymethyl-6j11-dioxonaphthacene was produced as follows.

(1) (IS)-cis-3-acetoxymethyl-1,2,3,4°6.11- in tetrahydro78Qal
hexahydro-1,3,5,12-tetrahydroxy-
A solution of 1.0y of 6,11-dioxonaphthacene was heated to -5°C.
2.3, 4.6 in 10 ml of dichloromethane.
-tetradeoxy-3-trifluoroacetamide-α
-L-7. Leohexopyranosyl chloride 0.7. !
ii' was added. The mixture was stirred while a solution of 0.5 g of silver trifluoromethanesulfonate in tetrahydrone run 15#I/was added dropwise over 20 minutes. The mixture was stirred at -5°C for 0.5 h, then poured into 300 ml of 10% potassium bicarbonate and dichloromethane added each iooog.
Extracted 4 times. The dichloromethane extract was dried over anhydrous sodium sulfate and evaporated to give a red gum, which was purified on silica gel with ethyl acetate/n-
Purified by column chromatography using hexane (1:1 vol/vol).

In addition to 300 μl of unreacted dioxonaphthacene starting material, (IS)-cis-3-acetoxymethyl-1-[(2,3,4,6-tetradeoxy -3-trifluoroacetamide-α-L
-threohexopyranosyl)oxy)-1,2,3,4
, 500η of 6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxonaphthacene was obtained;
[α]'','=+206.9° (c==0.05% in dioxane).

(11) Compounds obtained according to the above section 0.5,! 1
7 to dichloromethane 200117 and methanol 200
jlIC was dissolved and enough 0.1M aqueous sodium hydroxide solution was added to make it dark purple. The solution was stirred at room temperature for 6 hours, and the reaction was quenched by the addition of acetic acid, returning the color to orange-red. The resulting solution was diluted with 250 d of water and extracted four times with 100 d of dichloromethane each. The combined dichloromethane extracts were dried over anhydrous sodium sulfate and evaporated to give an orange crystalline solid.

Crushed with diethyl ether, melting point 240-242℃
(IS)-cis-1-[(2,3,4,
6-tetradeoxy-3-trifluoroacetamide-
α-L-threohexopyranosyl]oxy)-1,2,
3,4,6,11-hexahydro-3,5,12-trihydroxy-3-hydroxymethyl-6,11-dioxonaphthaseyO,36,! 7; [(Xl”=
+228.1° (c = 0.05 factor, in dioxane).

Example 11 (a) (Is)-cis-1-((2,3,4,6-tetradeoxy-3-trifluoroacetamide-α-L-
threhexopyranosyl)oxy]-1,2,3,4,
6,11-hexahydro-3゜5.12-)IJ hydroxy-3-hydroxymethyl-6,11-dioxonaphthacene 0.59t - dissolved in 75t+l of dry pyridine,
Pyridine-3-carboxylic acid azide 1. Added Og. The mixture was heated to 70° C. for 1 hour, cooled and the solvent was removed by evaporation. Red residue in dichloromethane for 150s
uK dissolved and the solution was washed twice with 2M acetic acid each 100117, water 1001/ and 15q6 potassium bicarbonate until no more bubbling occurred. This solution was dried over anhydrous sulfuric acid (IJ), evaporated and the residue was evaporated onto silica gel, using as eluent first 10% acetone in dichloromethane to elute the impurities and then to elute the product. It was purified by chromatography using 5-functional methanol in ethyl acetate. The product-containing fractions were evaporated and the red residue was crystallized from methanol/diethyl ether to form (IS)-cis-1-1:(2,3,4°6-tetra Deoxy-3-trifluoroacetamide-
α-L-Threohexopyranosyl)oxo]-1,2,
3,4,6,11-3,5,12-)dihydroxy-6
, 11-dioxo-3-(3-pyridylcarbamoyloxy)methylnaphthacene 0.259 was obtained; [α)”=
+199.5° (c=0.05° in dioxane).

(b) Compound obtained according to section (a) in Example 9
Treated according to the method described in (b), except that 0.25M methanolic hydrogen chloride was added to ensure formation of the dihydrochloride salt. (IS)-cis-1-[(3-amino-2,3,4,6-tetradeoxy-α-L-threohexopyranosyl)oxo]- in the form of an orange powder with a melting point of 177-179°C (decomposition) 1, 2, 3, 4, 6, 11
-hexahydro-3゜5.12-3.5.12-)lihydroxy-6゜11-dioxo-3-(3-pyridylcarbamoyloxy)methylnaphthacene dihydrochloride 430~
obtained; [α”+2D.=+146.1°(c=0.0
5ch in methanol).

Example 2 (a) (Is)-cis-1-((2,3,6-drideoxy-3-trifluoroacetamido-4-〇-methyl-α-L-lyxohexopyranoyl)oxy)- 1,
2,3,4,6,11-hexahydro-3,5,12-
) 0.55.9 ml of dihydroxy-3-hydroxymethyl-6,11-dioxonaphthacene was dissolved in 50 m of dry pyridine and penzylisocyanate) 1. The mixture was heated to 65° C. for 45 minutes. Then an additional 0.3 g of pendylisocyanate was added and heating at 65° C. was continued for a further 1.5 hours. The mixture was then cooled and the pyridine was removed by evaporation. The red residue was purified by chromatography on silica gel using dichloromethane containing 20% acetone as eluent. After precipitation from dichloromethane by gradual addition of hexane,
(is)-cis- in the form of an orange powder with a melting point of 110-115°C
3-(pencylcarbamoyloxy)methyl-1-[(
2,3゜6-drideoxy-3-trifluoroacetamido-4-0-methyl-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,5 , 12-)rihydroxy-6,11-dioxonaphthacene 0.51 was obtained.

(b) Compound obtained according to clause (a) 0.55
(Is) in the form of an orange-red powder with a melting point of 167-170°C (decomposition).
-cis-1-C(3-amino-2,3,6-)lysooxy-4-0-methyl-α-L-lyxohexopyranosyl)oxy]-3-(benzylcarbamoyloxy)methyl-1, 2,3,4,6,11-hexahydro-3,5
, 12-trihydroxy-6,11-dioxonaphthacene hydrochloride 0.484y was obtained; [α:]”=+162
．． 3° (c=0.05° in methanol).

(IS)-cis-1-[(2,3,6-1lysooxy-3-trifluoroacetamido-4-〇-methyl-α-L-lyxohexopyranosyl) used as starting material in section (a) Oxy]-1゜2.3,4.6.11-
Hexahydro-3,5°12-trihydroxy-3-hydroxymethyl-6,11-dioxonaphthacene was prepared as follows: (1) (IS)-cis-3-acetoxy in tetrahydrofuran 320d. Methyl-1,2,3,4゜6.11-
hexahydro-1,3,5,12-tetrahydroxy-
6,11-Dioxonaphthacene - 4.0 g of solution was added to 2,3 according to the method described in Example 10 (+1)
．． 6-) Lysooxy-3-trifluoroacetamide-
4-0-Methyl-α-L-lyxohexopyranosyl chloride 3.2I and silver trifluoromethanesulfonate 2
．． Treated with Ol. After purification of the product by chromatography, unreacted dioxonaphthacene starting material 2
．． In addition to 0 g, (IS)-cis-3-acetoxymethyl-1-[(2,
3゜6-drideoxy-3-trifluoroacetamido-4-0-methyl-α-L-lyxohexine pyranosyl)
[oxy]-1,2,3,4,6,11-hexahydro-
2.42 g of 3j5,12-)rihydroxy-6.11-dioxonaphthacene was obtained; [α]”=+161.2°
(c=0.05 h in dioxane).

(11) 1.5 g of the compound thus obtained was treated according to the method described in Example 1o (+H), melting point 26
(IS)-cis-1-[(
2,3,6-drideoxy-3-trifluoroacetamido-4-0-methyl-α-L-lyxohexopyranosyl)oxy-1,2,3,4°6.11-hexahydro-3,5 , 11-trihydroxy-3-hydroquinemethyl-6,11-dioxonaphthacene 1.11.9 was obtained; [α]2°=+181.3° (c=o, 05ti, in dioxane) .

Example 13 (a) Following the method described in Example 1(a), (IS
)-cis-1.2,3,4,6.11-hexahydro-
1,3,5,12-tetrahydroxy-3-[[:2-
(methoxycarbonyl)ethyl [carbamoyloxy]
2. 1.0 g of methyl-6,11-dioxonaphthacene.
3.6-) Lysooxy-4-〇-p-nitrobenzoyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride 1.7,! Treated with i+.

After chromatography, in addition to 0.2.9 of the unreacted dioxonaphthacene starting material, (IS
)-cis-1-((2,3,6-)lysooxy-3-trifluoroacetamido-4-0-1)-nitrobenzoyl-α-L-lyxohexinepyranosyl)oxy]-1
,2,3,4,6,11-hexahydro-3°5.12
-) Lihydroxy-3-02-(methoxycarbonyl)
1.0 g of ethyl]carbamoyloxy]methyl-6,11-dioxonaphthacene was obtained, which was used without further purification.

(b) Compound 1 obtained according to clause (a). The OI was treated according to the method described in Example 1(b) and had a melting point of 13
(IS)-cis-1-[:
(2,3,6-)lysooxy-3-trifluoroacetamido-α-L-lyxohexopyranosyl)oxy]-
1,2,3,4,6,11-hexahydro-3,5,1
70.55 g of 2-trihydroxy-3-02-(methoxycarbonyl)ethyl]carbamoyloxy]methyl-6,11-dioquine naphtase was obtained: [α]”=++
55.3° (c = 0.05° in dioxane).

(c) Dissolve 0.5I of the compound obtained according to clause (b) in 10#I/tetrahydrofuran and add 0.1
It was added to 70ml of M aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 45 minutes and then the solution I)H was added with 2M hydrochloric acid.
Acidified until the value was approximately 7. Add 175 d of water,
This solution was extracted three times with 350 ml each of n-butanol. Distill 200 liters of the combined n-butanol extract.
The n-butanol layer was evaporated under vacuum to give an orange solid. This solid was mixed with methanol 251+1/
Suspended in 0.175M methanolic hydrogen chloride 2.5
Added d. After most of the solids dissolved, the solution was filtered and concentrated to 15m. While stirring, 250 d of anhydrous diethyl ether are added and the precipitated product is filtered off and dried under vacuum to give an orange-polymer with a melting point of 155-163°C (decomposition).
(IS)-cis-[(3-amino-2゜3
．． 6-drideoxy-α-L-lyxohexopyranosyl)oxy]-3-[(2-carboxyethyl)carbamoyloxycomethyl-1,2,3゜4.6.11-hexahydro-3,5, 12-) dihydroxy-6,11-
Dioxonaphthacene hydrochloride 0.25. ! got ii';
[α, :l! 0 = +125.6° (C = 0.05%,
in methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-1,3, used as starting material in section (a)
5,12-tetrahydroxy-3-[[2-(methoxycarbonyl)ethyl]carbamoyloxy]methyl-6
, 11-dioxonaphthacene was prepared as follows: (IS)-cis-1°2 in dry pyridine 12111j.
．． 3,4,6,11-hexahydro-5,12-dihydroxy-3-hydroxymethyl-6,11-dioxo-
1,3-naphthacenediylbenzene polone) 1. Q,
! iJ and methyl 3-incyanatopropione) 0
．． 88,! The solution of i' was stirred at room temperature for 4 days. The pyridine was removed by evaporation under reduced pressure and the red residue was dissolved in dichloromethane 6011/, 2-methyl-2,4-bentanediol 1.3311/ and glacial acetic acid 0.66. The mixture was then stirred at room temperature for 40 hours. This solution was diluted with 500 d of dichloromethane and washed four times with 150 d of sphagnum moss. After drying over anhydrous sodium sulfate, the solvent was removed by evaporation to yield a red crystalline product. Crush with diethyl ether to produce an orange with a melting point of 146-149°C.
Red crystalline (IS)-cis-1,2,3,4°6.1
1-hexahydro-1,3,5,12-tetrahydroxy-3-CC2-(methoxycarbonyl)ethyl]carbamoyloxy]methyl-6°11-dioxonaphthacene 0.84,9 was obtained; [α ]2D. =+113.9°
(c = 0.05% in dioxane).

Example Work 4 (a) According to the method described in Example 1 (a), (1s
)-cis-1,2,3,4,6,11-hexahydro-
1,3,5,12-tetrahydroxy-3-[[2-(
methoxycarbonyl)ethyl]carbamoyloxy]methyl-6,11-dioxonaphthacene 0.526.9'
was treated with 0.9 g of 3-chloroacetamido-2°3.6-drideoxy-4-0-p-nitrobenzoyl-α-L-lyxohexopyranosyl chloride. After chromatography, in addition to 0.146 g of unreacted dioxonaphthacene starting material, in the form of an orange powder (1s)
-cis-1-[(3-chloroacetamide-2,3゜6
-Drideoxy-4-0-p-nitrobensoyl α-
L-lyxohexopyranosyl)oxy]-1,2,3,
4,6,11-hexahydro-3゜5,12-trideoxy-3-[["2-(methoxycarbonyl)ethyl]
Carbamoyloxy]methyl-6,11-dioxonaphthacene 0.355. ! 9 was obtained and used without further purification.

(1)) Compound obtained according to clause (a) 0.35/
(1s)-cis-1 was treated according to the method described in Example 1(b) to give (1s)-cis-1 as an orange powder with a melting point of 135-145°C.
-[(3-chloroacetamido-2,3,6-)lysooxy-α-L-lyxohexopyranosyl)oxy]-1
,2,3,4,6,11-hexahydro-3,5,12
-) Lysooxy-3-[["2-(methoxycarbonyl)ethyl]carbamoyloxy]methyl-6,11-dioxonaphthacene 0.17779 was obtained; [α: 1%'
=+135.9° (c=0.0596, dioxane).

(C) 0.1 g of the compound obtained according to section (b) was suspended in 100 d of ethanol containing 50 da of thiourea. The mixture was heated under reflux for 26 hours, then cooled and the solvent removed by evaporation. Pour the residue into water 100dK
Dissolved and pH value adjusted to 3 with hydrochloric acid. This solution was extracted three times with 504 portions of dichloromethane and these extracts were discarded. The pH value of the aqueous phase was adjusted to neutral by the addition of dilute sodium bicarbonate and then extracted three times with 50 g each of dichloromethane containing 10 g of methanol. The combined extracts were dried over anhydrous sodium sulfate and evaporated.

The residue was dissolved in 20 mt7 of methanol and the solution was filtered. The furnace liquor was treated with 0.175M methanolic hydrogen chloride 1-, then 2501 d of dry diethyl ether and 100 d of n-hexane were added. The precipitated product was filtered off and dried under vacuum to form (IS)-cis-[(3-amino-2,3,6-
Dorideoxy-α-L-lyxohexopyranosyl)oxy]-1゜2.3.4,6.11-hexahydro-3,
5゜12-trihydroxy-3-[:[2-(methoxycarbonyl)ethyl]carbamoyloxy]methyl-6
tll-dioxonaphthacene hydrochloride 57Wli was obtained;
[α] Two. =+146.8° (c=0.05% in methanol).

Example 15 (IS)-cis-[(3-amino-2,3,6-drideoxy-α-L-lyxohexopyranosyl)oxy:]
-3-[:(2-carboxyethyl)carbamoyloxycomethyl-1,2,3,4゜6.11-hexahydro-3,5,12-)dihydroxy-6,11-dioxonaphthacene hydrochloride Dissolve 10μ in methanol 5d and add 0
．． 9.5 at of 175M methanolic hydrogen chloride was added. The solution was kept in the dark at 4°C for 48 hours, then 5Q water
I poured it into iu. Add acidic aqueous solution to dichloromethane 20ml 1C
Extracted twice and these extracts were discarded. The aqueous solution was adjusted to a neutral 1) H value by addition of hydrogen carbonate and extracted three times with 3 Qm/each of dichloromethane containing 10% methanol. The combined extracts were dried over anhydrous sodium sulfate and evaporated to give a red residue, which was dissolved in 2 ml of methanol and filtered. ν liquid 0.17
Treat with 5M methanolic chloride, ml of hydrogen chloride, then add 251 J of diethyl ether and 10-hexane. The precipitated product was filtered off and dried under vacuum to give (IS)-cis-1-[(3-amino-2,3
゜6-Drideoxy-α-L-lixohexopyranosyl]oxy)-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-3-02-(methoxycarbonyl)ethyl [carbamoyloxy]methyl-
6,11-dioxonaphthacene hydrochloride 6.1 was obtained, which was identical to the product obtained according to Example 14.

Example 16: 25ml of tetrahydrofuran and 151ml of dioxane
(IS)-cis-1,2,3°4.6 in a mixture of 1/
．． Example 1 ( 2,3,6-drideoxy-4-O-1 according to the method described in a)
)-nitrobenzoyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride 067g
Processed with.

After chromatography, 0.12 of the unresolved dioxonaphthacene starting material,! In addition to i+, (IS)-cis-1-[(2,,3,6-drideoxy-3-trifluoroacetamide-4-0-p
-Nitrobenzoyl-α-L-lyxohexopyranosyl)oxy]-1,2,3,4゜6.11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-3-[ 0.291.9 of [2-(propylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene was obtained.

(b) Compounds obtained according to section (a) in Example 1
(b), melting point 127-13
(IS)-cis-1-[(
2,3,6-)lysooxy-3-trifluoroacetamido-α-L-lyxohexinpyranosyl)oxy]-1
,2,3,4,6,11-hexahydro-3,5,12
-1-lihydroxy-6゜11-dioxo-3-[[(2
-(Propylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene was obtained; [α)”=+ 133.
3° (c=0.05% in dioxane).

(C) Compound obtained according to section (b) in Example 1
(c), melting point 152-16
(IS)-cis-1-[ as an orange-red powder at 2°C (decomposition)
(3-amino-2,3,6-)lysooxy-α-L-lyxohexopyranosyl)oxy11-1°2.3,4.
6.11-hexahydro-3,5゜12-trihydroxy-6,11-dioxo-3-CC2-Cpropylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene hydrochloride was obtained; [α: +20=+169 .5°(c
= 0.05% in yxpnor).

(is)-cis-1,'2,3,4,6,11-hexahydro-1,3,5,12-tetrahydroxy-6,11-dioxo-3 used as starting material in section (a) -[C2-(Propylcarbamoyl)ethyl]carbamoyloxy]methylnaquine was prepared as follows: (+)(Is)-cis-1,2,3,4,6°11-hexahydro- 1,3,5,12-tetrahydroxy-3
-[[2-(methoxycarbonyl)ethyl]carbamoyloxy]methyl-6,11-dioxonaphthacene0.
2I in 5QwJ of tetrahydrofuran containing 4 drops of glacial acetic acid.
Benzeneboronic acid inside is 0.0! The mixture was heated at 80°GK for 2 hours. The volume remaining after removing the solvent by evaporation is 8
d was obtained, and 0.1M sodium hydroxide aqueous solution 32t+
Added 7.

The mixture was stirred at room temperature for 2.5 hours and then acidified to an I)H value of 2 by dropwise addition of concentrated hydrochloric acid. Mix 200% water
ml and the product was diluted with n-butanol 1001,
Next, the mixture was extracted with 50 l of 1/Cn-butanol. The n-butanol extracts were combined and evaporated. The red crystalline residue was triturated with diethyl ether, filtered and (IS)-cis-3-[:(2-carboxyethyl)carbamoyloxitamethyl-1,2,3,4,6
, 11-hexahydro-5,12-dihydroxy-6,
0.2 g of 11-dioxo-1,3-naphthacenediylbenzene polone was obtained, which was used in the next step without further purification.

(11) 0.2 g of the compound obtained according to clause (1) was suspended in dichloromethane 44-, and 0.2 g of oxalyl chloride! ! and 2 drops of dimethylformamide were added. The mixture was stirred at room temperature for 2 hours while excluding moisture;
A red solution was obtained. The solution was cooled to 0° C. and 0.49 g of n-propylamine was added.

After 2.5 hours, the solution was diluted with 10/11 dichloromethane and the resulting solution was washed with 50 d1 of 10% hydrochloric acid and then 5 Qd of water. After drying over anhydrous sodium sulfate, the solution was concentrated to 20,117 and 2 -Methyl-2,4-bentanediol 2d and 5 drops of glacial acetic acid were added.The solution was allowed to stand at room temperature for 52 hours, then dichloromethane l Q Q v+
Washed with 14 times 50 ml of water, dried over anhydrous sodium sulfate and evaporated to give a red crystalline solid. Disintegrated with diethyl ether, melting point 120-12
(IS)-cis-1,2,3, in the form of orange-red crystals at 5°C.
4,6゜11-hexahydro-1,3,5,12-tetrahydroxy-6,11-dioxo-3-[[:2-(
0.149 of flobylcarbamoyl)ethyl]carnocurmoyloxy]methylnaphthacene was obtained; [α]2°=
+86.9° (c=0.05°, in Tsumekisan).

Example 17 (a) (Is)-cis-1,2,3,4,6.

0.5 g of 11-hexahydro-1,3,5,12-tetrahydroxy-6,11-dioxo-3-[1:2-(propylcarbamoyl)ethyl]carno(moyloxycomethylnaphthacene) was dissolved in 39 d of dry tetrahydrofuran. A total of 1.0 g of 2.
3.6-) Lysooxy-4-0-p-nitrobenzoyl-3-trifluoroacetamide-α-L-arabinohexohyfunosyl chloride treatment. After chromatography on silica gel using ethyl acetate as eluent and then ethyl acetate containing 5% methanol, 0.165 g of unreacted dioxonaphthacene starting material was added to (IS)-cis -1-[(2,3,6-)lysooxy-3-trifluoroacetamido-4-0-p-nitrobenzyl-α-L-arabinohequinpyranosyl)
Oxy]-1゜2.3,4.6.11-hexahydro-
3,5゜12-trihydroxy-6,11-dioxo-
3-([2-(7'ropylcarno(moyl)ethyl]carbamoyloxy]methylnaphthacene and the corresponding β-
A mixture of isomers 0.173.9 was obtained.

(b) The mixture of glycosides obtained according to section (al) was treated according to the method described in Example 1(b) to obtain the corresponding mixture of hydroxyglycosides. Separated by chromatography using a melting point of 232 to 235°
(IS)-cis-1-[(2
,3,6-drideoxy-3-trifluoroacetamido-α-L-arabinohexopyranosyl)oxy:]-
1,2,3°4.6.11-hexahydro-3,'5.
12-trihydroxy-6,11-dioxo-3-[:
(2-furobylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene; [α]”=+186.0°(
c=0.05% in dioxane); and melting point 200~
(IS)-cis-1 in the form of orange crystals at 209°C (decomposition)
-((2,3,6-)lysooxy-3-trifluoroacetamide-β-L-arabinohequinpyranosyl)oxy]-1,2,3,4°6.11-hexahydro-3
,5,12-)dihydroxy-6,11-dioxo-3
-[[2-(propylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene; [α]■=+202.
0° (c=0.05q6 in dioxane) was obtained.

(c) The α-glycoside obtained according to section (b) is treated according to the method described in Example 1(C) and has a melting point of 15
(IS)-cis-1-[(3-amino-2,3,6-)lysooxy-α in the form of an orange powder at 8-165°C (decomposition).
-L-arabinohexopyranosyl)oxy:]-]1.
2.3,4,6.11-hexahydro 3.5.12-1
-dihydroxy-6,11-dioxo-3-[[2-(
propylcarbamoyl)ethyl [carbamoyloxy]
Obtained methylnaphthacene hydrochloride [α]” = + 198
．． 8° (c = 0.05 h in methanol).

Example 18 (a) Tetrahydrofuran ((IS) in '19d)
-cis-1,2,3,4,6,11-hexahydro-1
,3,5,12-tetrahydroxy-6,11-dioquine-3-[1(2)-(phenylcarbamoyloxy)
A solution of 690 ml of ethyl naphthacene was stirred at -2°C under a nitrogen atmosphere, and 11.5 P of tetrahydrofuran was added. 2.3.6-1 Solution of lysooxy-4-0-p-nitrobenzoyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride 698~ in diethyl ether-9Ill A solution of 6141 ng of silver lomethane sulfonate was added simultaneously over 1 hour.

The mixture was stirred for a further 1 hour at -2°C, after which a further 698q of the above chlorosugar in 11.5*/tetrahydrofuran and 614~ of silver trifluoromethanesulfonate in 19d diethyl ether were added over 30 minutes. . The mixture was stirred for a further 2.5 hours at -2°C,
It was then poured into a mixture of 365 d/ml of 10% potassium hydrogen carbonate solution and 154 ml/ml of ethyl acetate. Filter this mixture and
The filtrate was transferred to a separatory funnel and the layers were separated. The organic extract was washed twice with Sphagnum 5181/, dried over anhydrous sodium sulphate and evaporated to give a red oil. This oil was applied to a column of 200 g of silica gel using ethyl acetate/60~ as the eluent.
80℃ petroleum ether (1:2, vol/vol) 1
41 and ethyl acetate/60-80℃ petroleum ether (2:
1, vol/v) 300 d. After crystallization from dichloromethane, it appears as bright orange crystals with a melting point of 198-204°C (IS
)-cis-1-[(2゜3.6-)lysooxy-3-trifluoroacetamido-4-0-p-nitrobenzoyl-α-L lyxohexinepyranosyl)oxy]-1,2
, 3゜4.6.11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-3-[1(6)=
(Phenylcarbamoyloxy)ethylsinaphthacene 7
10~ was obtained; [α120=o° (c=0.1, in dioxane).

(b) Compound 6901' obtained according to clause (a)
9 was dissolved in dichloromethane 51 and this solution was diluted with methanol 525. The resulting solution was cooled to 0 °C,
8.5 mL of an aqueous solution of 0.1M hydroxide was added. The deep purple mixture was stirred at 0° C. for 30 minutes, then glacial acetic acid was added dropwise until the solution turned bright red. This solution was concentrated under vacuum to about 100 gu, then 900 g of water
and extracted twice with ethyl acetate 20011/. The combined extracts were dried over anhydrous sodium sulfate and evaporated. The crude product was purified by 125% silica gel. ! ; I column with 1.5 t of dichloromethane and acetone/dichloromethane (5:95, vol/vol) as eluent.
11 and acetone/dichloromethane (10:90, v
ol/vol) It was purified by chromatography.

(IS) as a bright red solid with a melting point of 158-162°C
cis-1-[,(2,3,6-)lysooxy-3-trifluoroacetamido-α-L-lyxohexinepyranosyl)oxy:]-1,2,3,4゜6.11-hexahydro -3,5,12-)dihydroxy-6,11-dioxo-3-[1(2)-(phenylcarbamoyloxy)ethylsinaphthacene 240 mg was obtained; [α]”=+
216° ((=0.1 yen, in dioxane).

(C) A solution of compound 350 #v obtained according to section (b) in 7 d of tetrahydrofuran was added to 55 ml of 0.1 M aqueous sodium hydroxide solution and the deep purple mixture was stirred at room temperature under nitrogen for 30 min. The solution was adjusted to an I)H value of 8 by addition of 5M hydrochloric acid and the mixture was extracted 5 times with 8017 portions of dichloromethane.

The combined extracts were washed with 8 Qd of water, dried over anhydrous sodium sulfate, and evaporated to give a red gum.

This rubber was dissolved in a mixture of 101 dichloromethane and 1d methanol. 0.25M methanolic hydrogen chloride 2
．． 11d followed by 53m of diethyl ether. This mixture was left at 0°C overnight. The product is separated, washed with diethyl ether and dried under vacuum, melting point 169~
(IS)-cis-1-(
(3-amino-2,3,6-)lysooxy-α~L-lyxohexopyranosyl)oxy]-1,2,3,4,6
.

11-hexahydro-3,5,12-)dihydroxy-
6,11-dioxo-3-[1(8)-(phenylcarbamoyloxy)ethyl]naphthacene hydrochloride 215mr
[α] bell=+217° (c=0.1% in methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-1,3, used as starting material in section (a)
5,12-tetrahydroxy-6,11-dioquine-3
-[1(2)-(phenylcarbamoyloxy)ethylsinaphthacene was prepared as follows: (1)(IS)-cis-1,2,3,4,6,11-hexahydro-5 , 12-dihydroxy-3-[1(8)
-(hydroxy)ethyl]-6.11'-dioquine-1
, 3-naphthacenediylbenzene polone) 0.70.
9 was dissolved in pyridine 80d, and phenyl isocyanate)
5101Y was added. The mixture was heated to 60° C. for 3 hours, cooled and the solvent was removed by evaporation. The residue was poured into dichloromethane 1611, a part of the colorless insoluble substance was separated, and the solution was further diluted with dichloromethane 144d. The resulting solution was diluted with 8Q trl of 2M hydrochloric acid and 3Qm water.
(IS)-cis-1,2,3,4,
6゜11-hexahydro-5,12-dihydroxy-6
, 11-dioxo-3-[1(■-(phenylcarbamoyloxy)ethyl)-1,3-naphthacenediylbenzene boronate 900 ml, which was used without further purification.

(11) The benzene boronate obtained according to clause (1) is dissolved in a mixture of 70 fu of dichloromethane, 13 m of 2-methyl-2,4-bentanediol and 3.5 d of glacial acetic acid, and the solution is heated under reflux to 2.5 d of glacial acetic acid. heated for an hour. The solution was then cooled, washed four times with 170 g of water, dried over anhydrous sodium sulfate, and evaporated. The residue was triturated with 2 Qm/diethyl ether, filtered, melting point 229.5~
(IS)-cis-1,2,3, in the form of red crystals at 234℃
4,6,11-hexahydro-1,3,5,12-tetrahydroxy-6,11-dioxo-3-[1(8)-
(Phenylcarbamoyloxy)ethyltunaphthacene 6
Obtained 10■; [α)”=+205°(c=0.LL1
6 in dioxane).

(IS)-cis-1,2,3,4,6,11-hexahydro-5,12 used as starting material in section (1)
-dihydroxy-3-[1■-(hydroxy)ethyl:
]-]6.11-Dioxo 1,3-naphthacenediylbenzene boronone 1d Prepared as follows: (S)- in 250 gIl of dry tetrahydrofuran
3'-acetyl-i/, 2/, 3/, 4/-tetrahydro-3'-hydroxy-5'+8'-dimethoxyspiro [1,3-dithiolane-2,1'-naphthalene]
A solution of 10.0 g was cooled to -78°C and 1.12.9 g of lithium aluminum hydride in 75 m diethyl ether was added.
solution was added over several minutes. The mixture was stirred for 30 minutes at -78° C. under nitrogen and then further treated with lithium aluminum hydride i, i in 75 m diethyl ether.
2 g was added. After a total reaction time of 45 minutes, 250 d of 2M hydrochloric acid was carefully added to the mixture, followed by 750 d of water.
Tnl was added. Mixture with dichloromethane 600ml each
1 and the combined extracts were washed with 300 l/l of water, dried over magnesium sulfate, and evaporated to give (3'5)-1',2' as a colorless gum and a mixture of isomers.
,3'.

4'-tetrahydro-3'-hydroxy-3'-[1-
(hydroxy)ethyl) -5',8'-dimethoxyspiro[1,3-dithiolane-2,1'-naphthalene]
was obtained and used without further purification.

The product obtained according to the above section was dissolved in 100 ml of pyridine and 15 ml of acetic anhydride was added to this solution. This mixture was left at room temperature overnight. Add 200 g of ice to the mixture. ! 9
, then 200 ml of 6M hydrochloric acid was added. The resulting mixture was extracted three times with 209 ml each of dichloromethane. The combined extracts were washed with 2M hydrochloric acid 20011/200 d water, dried over magnesium sulfate and evaporated to give (3'S) -3'-[1-
(acetoxy)ethyl]-1,2,3,4-tetrahydro-3'-hydroxy-57, S/-dimethoxyspiro[1,3-dithiolane-2,1'-naphthacene 111
．． 6.9' was obtained and used without further nl production.

The product obtained according to the above section was mixed with tetrahydrofuran 1
15111/, and this solution was diluted with methanol 1.15
and 36 ml of mercuric oxide in a mixture of 10 Q ml of water
．． 7 N and 36.7 fl of mercuric chloride were added over 10 minutes to a stirred suspension. The mixture was stirred at room temperature for 1.75 hours, then concentrated under vacuum to approximately half its volume. The resulting mixture was mixed with 1.57 t of dichloromethane.
and then filtered. Solution F was washed three times with 1 t of sphagnum moss, dried over magnesium sulfate, and evaporated to give (38)-3-(1-(acetoxy)ethyl]-1.2,3 as a colorless oil and a mixture of isomers. 8.2μ of 4-tetrahydro-3-hydroxy-5,8-dimethoxy-1-oxo-naphthalene was obtained, which was used without further f# preparation.

The product obtained according to the above section was mixed with tetrahydrofuran 4
25d, and 1.9 g of boron hydride was added to this solution. This mixture was heated at room temperature under nitrogen for 2 hours.
Stir for an hour. An additional 1.9 g of sodium borohydride was added to the mixture and stirring continued for an additional hour. To this mixture was gradually added 15 Qsl of 2M hydrochloric acid, and then extracted three times with 1601 parts each of dichloromethane. Add the combined extract to 50% water.
1, dried over magnesium sulphate and evaporated.

The residue was dissolved in 500 d of toluene, and benzeneboronic acid 4
．． 56. ! 1111)-) Luenesulfonic acid 0.16
g and 0.5 ml of glacial acetic acid were added. The mixture was stirred at room temperature under nitrogen overnight, then washed twice with 100 g each of 10% potassium bicarbonate solution, dried over magnesium sulphate and evaporated to give a colorless oil, 9.5 g. The crude product obtained was dissolved in 100ml of diethyl ether and the mixture was stirred at room temperature for 1 hour. After filtration, melting point 176
~179°C white crystalline (IS)-cis-3-C1 (
[α]
20=+65.5° (c=0.1° in chloroform). The mother liquor was concentrated to 20111/ and filtered to give a second crop of 2.10I. Evaporate the second mother liquor to a residue 3.
4g of Ligen was obtained, which was partially separated by column chromatography, and then fractionally crystallized to obtain a product with a melting point of 148~
(IS)-cis-3-[(Is
)-(acetoxy)ethyl”]-1,2゜3.4-tetrahydro-5,8-dimethoxy-1゜3-naphthacenediylbenzeneboronate at 1%; [α:l”=+22
．． 8° (c = 0.1° in chloroform).

A solution of ceric nitrate/monium 11,94.9 in 200 d of water was prepared from the above (18)-cis-3-[(IR)-(acetoxy)ethyl] 1,2,3.4 in 200 d of acetonitrile. -Tetrahydro-5,8-dimethoxy-1,3-naphthacenediylbenzene boronate 4.329 was added over 5 minutes to the stirred solution. The mixture was stirred for a further 5 minutes at room temperature and then poured into 1 t of water. The resulting mixture was diluted with 270 d of dichloromethane 4 times.
Extracted twice, the combined extracts were washed with 270 R1 of water, dried over magnesium sulfate, evaporated, and a yellow oil (I
S)-cis-3-[(IR)-(acetoxy)ethyl)
-1j2#14t5.8-hexahydro-5,8-dioxo-1,3-naphthalenediylbenzene boronate was obtained and used without further purification.

Trans-1,2-diacetoxy-
2.40 g of 1,2-dihydrobenzocyclophtene was added and the mixture was heated to 140° C. for 3 hours under a nitrogen atmosphere. The solution was cooled to NIL, the solvent was removed by evaporation, yielding a yellow crystalline product (7%), which was washed with diethyl ether and filtered with a sieve to give (Is)-silica as yellow crystals with a melting point of 175-184°C. , (-3-r(IR)-(7c)*c)ethyl]-1,2,3,4,5,12-hexahydro 5,12-dioxo-1,3-naphthacenediylbenzeneboronate 3 .6.9; [α]20=
+147.5° (c=0.1° in chloroform).

3.6 g of the compound obtained according to the above section was dissolved in a mixture of 175 ml of dry pyridine and 9 Qm of acetic anhydride. 175 my of Palladium 10 on carbon was added and the mixture was hydrogenated at room temperature and atmospheric pressure for 1 hour. The catalyst was separated from the furnace 1- and the filter cake was washed with dichloromethane. The combined furnace liquid was evaporated, and the residue was crushed with 5Qm of diethyl ether and filtered to give a melting point of 25.
(IS)-cis-5,1 as a light brown solid at 6-259°C
71 g4 of 2-diacetoxy-3-[(IR)-(acetoxy)ethyl]-1,2,3,4-tetrahydro-1,3-naphthacenediylbenzeneborone-1-3 was obtained.

The compound prepared according to the above section was dissolved in a mixture of glacial acetic acid 216d and acetic anhydride 68j. Add 2.88.9 g of finely ground chromium trioxide and stir the mixture at room temperature to 1.88 g.
Stirred for 8 hours. The mixture was poured into 620 il of water and the resulting suspension was dissolved in 320 il of dichloromethane with 4 (i
,]Extracted. The combined extracts were diluted with 450 ml of water each.
Washed twice, dried over magnesium sulphate and evaporated. The residue was triturated with 50 m of diethyl ether, filtered, and gave (I
S)-cis-5゜12-diacetoxy-3-[(IR)
-(acetoxy)ethyl) -1,2,3,4,6,1
1-hexahydro-6,11-dioxo-1,3-su7
Tasendiylbenzene boronate L77p was obtained.

A solution of the compound obtained according to the above section in dichloromethane 340 JRI was cooled to -78°C. A solution of 7 g of boron trichloride in dichloromethane 28117 was added and the mixture was stirred and warmed to 0° C. for Z5 hours.

The mixture was poured into ice-cold 2M hydrochloric acid 3401+Il and the layers were separated. The aqueous layer was extracted twice with 280 ml each of dichloromethane and the combined organic solutions were washed twice with 25011 Il each of water, dried over magnesium sulfate and evaporated to give the crude (IS)-cis- 3-[(IR)-(acetoxy)ethyl]-1,2,3,4,6,11-1-
(xahydro-5゜12-dihydroxy-6,11-dioxo-1゜3-naphthacenediylbenzeneborone) 1
．． 7 g was obtained, which was used without further cutting.

1.2 g of the compound prepared according to the above section was dissolved in a mixture of 1201111 dichloromethane and 120 ml methanol. 0.1M sodium hydroxide aqueous solution 48ml
was added, the resulting deep purple solution was heated under reflux for 3 hours, the mixture was allowed to cool, and glacial acetic acid was added until the solution turned bright red. The solution was poured into 480 ml of water and the resulting mixture was extracted twice with 240 ml of dichloromethane%. The combined extracts were washed with 360 ml of water, dried with anhydrous sulfuric acid sulfur ram, evaporated, and left as a red gum (1 s
)-cis-1゜2.3,4,6.11-hexahydro-
5,12-dihydroxy-3-[1(R)-(hydroxy)ethyl, :l-6,11-dioxo-1,3-naphthacenediylbenzene borone) 0.70μ was obtained, and this was further added. It was used without purification.

Example 19 (is)-cis- in tetrahydro7ran 5Qm/
1,2,3,4,6,11-hexahydro-1,3fs
, 1z-tetrahydroxy-6,11-dioxo-3-
[1st track - (phenylcarbamoyloxy)ethyl] A solution of 489 rtry of naphthacene was added to
2.3.6 in 12 m tetrahydrofuran with stirring at °C.
-) Lysooxy-4-0-p-nitrobensoyl-3-
) +7 Fluoroacetamido-α-L-arabinohexopyranosyl chloride 492 ~ and trifluoromethanesulfone R silver in diethyl ether 8d 282 mg
solutions were added simultaneously over a period of 1 hour. one or two parts of the mixture
After stirring for a further 2 hours at <RTIgt;C,</RTI> additional 247 ~ of the above chlorosugar in 12 ml of tetrahydrofuran and 141 kg of silver trifluoromethanesulfonate in 4 ml of diethyl ether were added over a period of 40 minutes. The mixture was stirred for a further 30 minutes at -2°C and then added with 10% sodium bicarbonate solution.
Pour into a mixture of 60 ml and 125 d of ethyl acetate.

The mixture was filtered, the filtrate was transferred to a separatory funnel, and the layers were separated. The organic extract was washed twice with 350 ml of sphagnum moss, dried over anhydrous sodium sulfate and evaporated. The crude product was passed through a column of 75 g of silica gel with ethyl acetate/petroleum ether (1:2, vol.
/vol) 800- and ethyl acetate/60-80
Purified by chromatography using 1501 °C petroleum ether (1:1, vol/vol). Together with the unreacted dioxonaphthacene starting material 2somy, (IS)-cis-1-
C(2,3,6-drideoxy-3-trifluoroacetamido-4-O-p-=)lobenzoyl-α-L-arabinohequinpyranosyl)oxy]-1,,2,3,4
゜6.11-Hexahydro-3,5,12-trihydroxy-6,11-dioxo-3-[1(R)-(phenylcarbamoyloxy)ethyl]naphthacene 360~ was obtained; [α]%'= +298° (C=0.1% in dioxane).

(b> Compound i obtained according to section (a), oss
g to dichloromethane 9TR1 and methanol 8251/
suspended in a mixture of 12.6 a/ml of an aqueous solution of 0.1 M hydroxide) was added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 30 minutes. Glacial acetic acid was added until the solution turned red, then the solution was concentrated under vacuum. The residue was treated with 1.25 t of water and the mixture was treated with 300 t each of ethyl acetate.
Extracted twice. The combined ethyl acetate extracts were dried over anhydrous sodium sulfate and evaporated. The product was transferred to a column of silica gel 200I using 2 t of dichloromethane and acetone/dichloromethane (5:95,
vol/vol)2 and acetone/dichloromethane (
Purified by chromatography using 10:90, vol, /vol) 41. Melting point 217-220
(IS)-cis-1-[(2,3,6
-Drideoxy-3-trifluoroacetamide-α-
L-arabinohequinpyranosyl)oxy]-1,2,3
,4,6,11-hexahydro-3゜5.12-trihydroxy-6,11-dioxo-3-C1 mono(phenylcarbamoyloxy)ethyl]naphthacene 580#v
I got it.

(C) A solution of 560 Ing of the product obtained according to paragraph (b) in 12 m of tetrahydrofuran was added to 901 l of 0.1 M aqueous sodium hydroxide solution and the mixture was stirred at room temperature under nitrogen atmosphere for 30 minutes. The solution was adjusted to a pH value of 8 by addition of 2M hydrochloric acid and dichloromethane 13
Extracted 5 times with 0-. The combined dichloromethane extracts were washed with 130 d of water, dried over anhydrous sodium sulfate,
Evaporation gave a red gum. This rubber was dissolved in a mixture of 1611 l of dichloromethane and 2 ynl of methanol,
Add this solution to 0.25M methanolic hydrogen chloride 3.411
/, then treated with 100 d of diethyl ether. After standing overnight at 0°C, the product was removed and dried under vacuum to give (IS)-cis-1-((3-amino-2,3,6 -) Lysooxy-
α-L-arabinohequinpyranosyl)oxy: l-1,
2,3,4,6,11-hexahydro-3,5,12-
Trihydroxy-6,11-dioxo-3-[1(2)
-(phenylcarbamoyloxy)ethylfunaftacene hydrochloride 250 WIg was obtained; [α]”=+271°(c
= 0.1 h in methanol).

Example 20 (a) (IS)-cis-1-[ in pyridine 15d
(2,3,6-)lysooxy-4-0-methyl-3-trifluoroacetamido-α-L-lyquinhexopyranosyl)oxy]-1,2,3,4゜6.11-hexahydro-3 ,5,12-)lihydroxy-3-(2-hydroxyethyl)-6゜11-dioxonaphthacene 200
1901 ng of phenyl isocyanate) was added to the solution of 1,901 ng of phenyl isocyanate, and the mixture was stirred at 60° C. for 40 minutes under nitrogen. The solvent was removed under vacuum and the residue was dissolved in dichloromethane 501
17 and the suspension was filtered to remove the insoluble 1 product. The furnace liquor was diluted with 3 Q ml of dichloromethane and the solution was diluted twice with 5 Q d of 2M hydrochloric acid and 5 times each with water.
Washed twice with 011+7, dried over anhydrous sodium sulfate and evaporated to give an orange gum 240~.

This gum was crystallized from a mixture of dichloromethane and diethyl ether as a bright red solid with a melting point of 160-170°C (IS)-cis-1-((2).

3,6-1lysooxy-4-0-methyl-3-trifluoroacetamido-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-3,5 ,12-trihydroxy-6,11-dioxo-3-[2-(phenylcarbamoyloxy)ethyl]
Su7tasen124■wo4fc: [1%'=+161
°(c = 0.05'ir, dioxane). The mother liquor was evaporated and the residue was purified on a column of silica gel 20.9 d with dichloromethane 800 d and acetone/dichloromethane (5:95, vol/vo J) as eluent.
ml was further chromatographed to obtain the above product 61W9.

(b) Compound 10811 obtained according to clause (a)
v was dissolved in tetrahydro7ran 1dK. 0.1 M aqueous sodium hydroxide solution 15- was added and the deep purple solution was stirred at room temperature under nitrogen for 95 minutes. solution to 0.2
A pH value of 8 was adjusted by addition of M. hydrochloric acid and then extracted 5 times with 25 ml of dichloromethane each. The combined extracts were washed twice with 100 g each of water, dried over anhydrous sulfuric acid, and evaporated to give an orange rubber. This rubber was dissolved in 2.0 mK dichloromethine, and the solution was cooled to 0°C. Add 0.631j of 0.25M methanolic hydrogen chloride and then diethyl ether 201+7 and reduce the mixture to 0.631j and then diethyl ether 201+7
It was kept overnight at °C. The product was filtered off, washed with 8d diethyl ether and dried under vacuum. Melting point 183-187
(IS)-cis-1-[(3-
Amino-2,3,6-)lysooxy-4-〇-methyl-α-L-lyxohexopyranosyl)oxy: l-1,2
,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-3-[2-(phenylcarbamoyloxy)ethylfunaftacene hydrochloride 9
27v was obtained; [α)'7=+193° (c=0.05
H, in methanol).

(IS)-cis-1-C(2,3,6-)lysooxy-4-〇-methyl-3-trifluoroacetamido-α-L-lyxohexopyranosyl) used as starting material in section (a) Oxy)-1゜2.3,4,6.11-
Hexahydro-3,5゜12-)lihydroxy-3-(
(2-Hydroxyethyl)-6,11-dioxonaphthacene was prepared as follows: (f) (IS) in 79,783 ml of Tet5 human ry.
-cis-3-(2-acetoxyethyl)-1,2゜3.
4,6. ]1-hexahydro-1,3j5゜12-tetrahydroxy-6,11-dioquinaphthacene 7'OO
A solution of 2.3.6-drideoxy-4- in tetrahydrofuran 131 was stirred at -5.degree. C. under a nitrogen atmosphere.
0-Methyl-3-trifluoroacetamide-α-L-
A solution of 562 ml of lyxohexopyranosyl chloride and 733 ml of silver trifluoromethanesulfonate in 22 ml of diethyl ether was added simultaneously over a period of 7 minutes.

After the mixture was stirred for a further 160 minutes, a further 271 to 129 of the above chlorosugars in 7 ml of tetrahydrofuran and 370,129 of trifluoromethanesulfonic acid in 1 ml of diethyl ether were added over a period of 3 minutes. The mixture was stirred for a further 70 minutes at -5° C. and poured into a mixture of 500 d of 10% sodium bicarbonate solution and 350 ml of ethyl acetate. The mixture was FA'd, Part F was transferred to a separatory funnel, and the layers were separated. The aqueous solution was extracted with 80w1 of ethyl acetate, and the combined organic extracts were washed three times with water and 5001w each, dried over anhydrous sodium sulfate, and evaporated to give an orange rubber. This rubber was passed through a column of 10M silica gel using ethyl acetate at 760-80°C as an eluent, petroleum ether (1:
2, vol/vol) 3.25t% ethyl acetate/6
0-80℃ petroleum ether (1:1, vol/'vol
) and 1 t of ethyl acetate. (IS)-cis-3-(2-acetoxyethyl)-1-((2,3,
6-drideoxy-4-0-methyl-3-trifluoroacetamido-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-3゜5.12- ) Dihydroxy-6,11-dioxonaphthacene 758 was obtained; [α:]20=+139.5° (c=0.1% in dioxane).

(11) 600 ml of the compound obtained according to section (1) was dissolved in a mixture of 65 tl of dichloromethane and 651 tl of methanol. 0.1M hydroxide) IJium aqueous solution 5
, 0 m was added and the resulting dark purple solution was stirred at room temperature under nitrogen. After a total reaction time of 230 minutes and 300 minutes, additional 5-unit 0.1 M aqueous solutions of IJ hydroxide were added. After a total reaction time of 320 minutes, glacial acetic acid was added to the mixture until it returned to a bright orange color. The solution was poured into a mixture of 200 d of water and 100 d/l of dichloromethane and the layers were separated.

The organic extract was dried over anhydrous sulfuric acid and evaporated to give an orange gum. This rubber was passed through a column of silica gel 411 with 400 ml of dichloromethane as eluent and 11 acetone/dichloromethane (5:95, vol/vol).
) 1050 m, acetone/dichloromethane (10:9
0, vol/vol) 350 rl, 7+ tons/
Dichlorometh/(15;85, vol/vol) 375
M/, acetone/dichloromethane (30nia 0, vol.
/vol) 400 wrl, acetone/dichloro, lomethane (60:40, vol/vol) 375 m
Purified by chromatography using 250 ml of acetone and 250 ml of acetone.
1-((2,3,6-drideoxy-4-o-methyl-
3-Trifluoroacetamido-α-L-lyxohexopyranosyl)oxy)-1,2゜3.4.6.11-hexahydro-3,5,12-trihydroxy-3-(2
-hydroxyethyl)-6,11-dioxonaphthacene 210#v was obtained, which was used without further purification.

(IS)-cis-3-(2-acetoxyethyl)-1,2゜3.4,6 used as starting material in Section (1)
．． 11-Hexahydro-1,3,5°12-tetrahydroxy-6,11-dioxonaphthacene (S)-1' in dimethylformamide 285M1 was prepared as follows.

2/ , 3/ , i/-tetrahydro-3'-hydroxy-s/, s/-dimethoxyspiro [1
, 3-dithiolane-2,1'-naphthyl-3'-methyl p-toluenesulfonate 21° 4I to a solution of water 14
．． Added to a solution of 10.7 g of potassium cyanide in 5d.

The mixture was stirred at 90'C under nitrogen for 4 hours, then allowed to cool and poured into 1.91 g of water. The resulting mixture was extracted three times with 4,751 parts each of ethyl acetate, and the combined extracts were extracted with 1 part each of water.
Washed 4 times with 9t, dried over anhydrous sodium sulfate and evaporated. The residue was triturated with 100 d of diethyl ether and filtered to give (S)-1' in the form of a white crystalline solid with a melting point of 173-174.5°C.

13.4 g of 2/, 3/, 4/-tetrahydro-3'-hydroxy-57,S/-dimethoxyspiro[1,3-dithiolane-2,1'-naphthalene] a/-acetonitrile was obtained; [α ]','=-28.4' (c
= 0.5 coefficient, chloroform).

A solution of the compound obtained according to the above section in 18.0 kg/ml of tetrahydrofuran was mixed with 1.49 methanol and 1 ml of water.
46.4 I of mercuric oxide and 46.4 I of mercuric chloride in a mixture of 34d. ! ;' was added to the stirred suspension.

The mixture was stirred at room temperature for 40 minutes and then concentrated under vacuum to approximately A of its volume. The resulting mixture was diluted with 1.6t dichloromethane and filtered. The solid filter residue was washed with 1 t of dichloromethane. The combined solution F was washed three times with 1.5 tons of sphagnum moss, dried over anhydrous sodium sulfate, and evaporated. The residue was triturated with diethyl ether and filtered to give (S)-1,2,3,4-tetrahydro-3-hydroxy-5,8-dimethoxy-1-oxo as a white solid with a melting point of 160-162°C. -3-Naphthalene acetonitrile 8-01'fr obtained; [α]20=+
1s, oo (c='0.1ch, chloroform).

The compound prepared according to the above section was added to tetrahydrofuran
00d and add 1.0 lithium borohydride to this solution.
Add 785.9 to ζ. The mixture was stirred at room temperature under nitrogen for 80 minutes. The solvent was removed under vacuum and the residue was
260 ml of g6 ammonium chloride solution was added. The resulting mixture was extracted three times with 260 ml each of ethyl acetate, the combined extracts were washed with 260 ml of water, dried over anhydrous sodium sulfate and evaporated. Toluene 6 to the residue
Suspend in 50 ml of benzeneboronic acid 5.94. ! i
! and 0.20811 l of p-)luenesulfonic acid were added. The mixture was stirred at room temperature under nitrogen for 2 days, then Kl
Washed twice with 280 m each of O% potassium hydrogen carbonate solution,
Dry over anhydrous sodium sulfate and evaporate.

The residue was crushed with 50 m of diethyl ether, filtered offshore,
(IS)- in the form of a white crystalline solid with a melting point of 124-127°C
[α]”= +
57.3° (C=0.1, in chloroform).

Compound 8.7I, prepared according to the above section, was added to 40% of toluene.
The solution was stirred under nitrogen and cooled to 0°C. 24.9 ml of a 1.2M solution of diisobutylaluminum hydride in toluene was added and the mixture was stirred at 0° C. for 40 minutes. 400 sl of 2M sulfuric acid was gradually added to the mixture, which was transferred to a separatory funnel and the layers were separated. Add aqueous solution to ethyl acetate each 4 Q Q vrl
The extract was extracted twice with a toluene solution. The resulting solution was washed with saturated sodium bicarbonate solution 40014, dried over anhydrous sodium sulfate and evaporated to give (lS)-cis-3-(formylmethyl)-1 as a pale yellow gum.
,2゜3.4-tetrahydro-5,8-dimethoxy-1
, 3-naphthalenediylbenzene boronate 8, 35
, p was obtained and used without further purification.

The compound prepared according to the above section was added to tetrahydrofuran 2
40d, and in this solution add 1 part of sodium borohydride.
．． 17,! ;I was added. The mixture was stirred at room temperature for 1 hour and the solvent was removed under vacuum. 2M hydrochloric acid 21 to the residue
5d was added dropwise L7, and the resulting mixture was dichloromethane 20% each.
Extracted three times at 0 m. The combined extracts were washed with 200ml of water, dried over anhydrous sodium sulfate, and evaporated to give (IS)-cis-1,2,3,4-tetrahydro-3-(2-hydroxy) as a pale yellow gum. (ethyl)-5,8-dimethoxy-1,3-su7tacenediylbenzenepolone)
8.38 F was obtained and was used without further purification.

The compound prepared according to the above section was dissolved in pyridine 7100d and 13.2 #l/acetic anhydride was added. Store this solution at room temperature overnight, then ice 370. iir was added in portions. The mixture was acidified with 2M hydrochloric acid and extracted three times with 450ml each of dichloromethane. The combined extract liquid is 2M
Washed with 300 ml of hydrochloric acid and 450 ml of water, dried over anhydrous sulfuric acid (U) ram and evaporated. The crude product was passed through a column of silica gel 500.9 using ethyl acetate/n-hexane (2, vol/vol) as eluent.
chromatography using mp 94-95
(IS)-cis-3-(2-acetoxyethyl)-1,2,3,4-tetrahydro-5,8- as a white solid at ℃
5.995 g of dimethoxy-1,3-su7talendiylbenzene boronate was obtained; [α:]%'=+5L9゜(
c = 0.1 t in chloroform).

Benzene Polone prepared according to the above paragraph in Acetonide IJ Le 275d) 5.99,! Add 2 parts of water to the solution of i+
Ceric ammonium nitrate in 75d 16.57.
! 9 solution was added over 5 minutes. The mixture was stirred for a further 5 minutes at room temperature and then poured into 163 tons of water. The resulting mixture was extracted 4 times with 3704 portions of dichloromethane, and the combined extracts were washed with 370 portions of water, dried over anhydrous sodium sulfate, and evaporated to give (IS)-cis-3- as a pale brown oil. (2-acetoxyethyl)-1,2,3,4,5
, 5.22 g of 8-hexahydro-5,8-dioxo-1,3-naphthalenediylbenzene boronone) were added,
This material was used without further purification.

Trans-1,2-diacetoxy-
1,2-dihydrobenzocyclobutene 3.34,! 9
was added and the mixture was heated to 140° C. for 3 hours under a nitrogen atmosphere. The solution was cooled and the solvent was removed under vacuum. The residue was crushed with diethyl ether 30-1 and filtered 1-1.
(IS)-cis- as a yellow solid with a melting point of 150-153°C.
3-(2-acetoxyethyl) -1,2,3,4,5
゜12-hexahydro-5,12-dioxo-1゜3-
(naphthacenediylbenzene borone) 5.19I was obtained; [α) 20 = + 135° (c = 0.1 chi, in Rilowaform).

The compound prepared according to the above section was added to dry pyridine 275d.
and acetic anhydride 137.5j17.

10% palladium 275 on carbon was added and the mixture was hydrogenated at room temperature and atmospheric pressure for 1 hour. The catalyst was separated by F and the filter cake was washed with dichloromethane. The combined liquid F was evaporated, and the residue was crushed with 30 m of diethyl ether and filtered to give a melting point of 198 to 200°C.
(IS)-cis-5.12-diacetoxy-3-(2-acetoxyethyl)-1,2,3゜4-tetrahydro-1,3-naphthacenediylbenzeneborone) 4 as a pale brown solid. I got .1.

The compound prepared according to the above section was dissolved in a mixture of 240 ml of glacial acetic acid and 80 ml of acetic anhydride. 3.22 g of finely ground chromium trioxide was added, and the mixture was stirred at room temperature for 1 hour.
Stirred for 6 hours. The mixture was poured into 700 d of water and extracted 4 times with 360 ml/each of dichloromethane. The combined extracts were washed twice with 380 d each of water, dried over anhydrous sodium sulphate and evaporated. Dilute the residue with diethyl ether 3
(IS)-cis-5,12-diacetoxy-3-(2-acetoxyethyl)-1,2°3.4.6
．． 11-hexahydro-6,11-dioxo-1,3-
127 g of naphthacenediylbenzene poronate were obtained.

A solution of the compound prepared according to the above paragraph in dichloromethane 43081/ was cooled to -78°C. A solution of 2.5.9 liters of boron trichloride in 10 R/dichloromethane was added and the mixture was stirred and allowed to warm to 0° C. for 45 minutes. The mixture was poured into ice-cold 2M hydrochloric acid, and the layers were separated. The aqueous layer was extracted twice with 365 d each of dichloromethane, and the combined organic solution was washed twice with 300 d each of water.
Dry over anhydrous sodium sulfate and evaporate to give (IS)-cis-3-(2-acetoxyethyl)-1 as a red solid.
, 2,3,4,6,11-hexahydro-5゜12-dihydroxy-6,11-dioxo-1゜3-naphthacenediylbenzene poronate, 2.05 g was obtained without further purification.・Used for '.

The benzene poronate prepared according to the above section was dissolved in a mixture of 200 m dichloromethane, 40 m 12-methyl-2,4-bentanediol, and 4 m acetic acid, and the solution was heated under reflux for 2.5 hours.

The solution was then cooled, washed four times with 480 d each of water, dried over anhydrous sodium sulphate and evaporated. The residue is crystallized from a mixture of diethyl ether and n-hexane, filtered and gives a red solid with a melting point of 120-125°C (IS
)-cis-3-(2-acetoxyethyl) -1,,2
,3,4,6,11-hexahydro-1,3,5,12
-tetrahydroxy-6,11-dioxonaphthacene 1
．． 5 g was obtained; [α] also '=+110° (c=0.1 in dioxane).

In addition, the above (IS)-cis-3-(2-acetoxyethyl)-1,2,3,4-tetrahydro-5,8-dimethoxy-1,3-naphthalenediylbenzene poronate is produced as follows. It was also possible to: 3.3 g of 5Q dispersion of IJum (hydrogenated in mineral oil)
Dry dimethyl sulfoxide 35a was stirred under nitrogen.
Added to /. This mixture was heated at 70°C until hydrogen generation stopped.
It was stirred with After cooling to 0°C, dry tetrahydrofuran 3
511/ was added. (Is)-1',2',3',4'-tetrahydro-2'-hydroxy-5/,S/-dimethoxyspiro[1,3-dithiolane-2,4'- in 3Qm dry tetrahydrofuran naphthalene]
5.0 g of methyl 2/-carboxylate was added over 10 minutes. After stirring for 15 minutes at 0°C, the mixture was diluted with water'
200114 and acidified to pHH3O with hydrochloric acid. This solution was extracted five times with dichloromethane each IQQIII. The combined dichloromethane extracts were washed with 200 d of water, dried over magnesium sulfate and evaporated to give crude β-ketosulfoxide 5.5I as an orange gum.

The product obtained according to the above section was dissolved in 50 d of pyridine and 20 1/2 acetic anhydride, and the solution was stirred without stirring.
Cooled to ℃. 4-dimethylaminopyridine 0.25I
was added and the mixture was kept at 0° C. for 18 hours. The solution was then poured onto 300 g of crushed ice and left for 1 hour. The mixture was then extracted four times with 15011 portions of dichloromethane.

The combined extract was mixed with 50,011 liters of water and 5,001 liters each of 2M hydrochloric acid.
1 twice, 500 d of water and 500 d of 10% potassium bicarbonate solution. After drying over anhydrous sodium sulfate, the solvent was removed by evaporation and a dark yellow gum was obtained,
This material was dissolved in 100 ml of dry tetrahydrone run. This solution was dissolved in 2.5 mj of lithium aluminum hydride in 100 mj of O'GIC-cooled tetrahydrofuran.
1i of the stirred mixture. After the addition was complete, the mixture was brought to room temperature, stirred at this temperature for 1 hour, and then heated under reflux for 1 hour. After cooling to 0°C, the reaction was stopped by carefully adding 2o1 of water followed by 200d of 2M hydrochloric acid.

The mixture was extracted four times with 150 ml each of dichloromethane, and the combined extracts were washed with 200 d of 2M sodium hydroxide solution and 200 d of water. After drying, the solvent was removed by evaporation and the residue was chromatographed on silica gel using ethyl acetate/n-hexane (1:1, vol/vol) and then ethyl acetate as eluent. After evaporation of the solvent, the stereoisomer mixture 1', 2' forms an orange foam with a melting point of 80-95°C.

3/, 4/-tetrahydro-3'-hydroxy-5',
8'-dimethoxyspiro[1,3-dithiolane-2,1
'-Naphthalene m1-3'-(Is)ethane-1,2(
R8)-diol 2.17. Obtained f2: [α] Back=-
119° (c=0.5%, in Clef form).

The diol obtained according to the above section was converted into benzeneporonic acid 0
．． 35p and 100d of ethyl acetate containing 2 drops of acetic acid. After heating to 70° C. for 30 minutes, the solvent was removed by evaporation, yielding 1.15 g of yellow gum, which was dissolved in pyridine 251. The solution was cooled to 0° C. and treated with 0.6 g of mesyl chloride. Bring the mixture to 0°C
It was held for 8 hours and then the solvent was removed by evaporation. The residue was dissolved in a mixture of 10 tons of dichloromethane, 2111 tons of 2-methyl-2,4-bentanediol and 0.5 tons of acetic acid. After standing for 2 days at 20°C, the mixture was diluted with 751 ml of dichloromethane and the solution was diluted with 75 ynl of sphagnum moss.
Washed twice. After drying, the solvent was removed by evaporation to obtain a pale yellow gum-like crude mesylate.

The product obtained according to the above section was converted into tetrahydrofugin 2
01117, and 100 ml of 0.5M aqueous sodium hydroxide solution was added. After stirring for 6 hours, the solution was extracted 6 times with 59 d each of dichloromethane, and the combined extracts were dried and evaporated to obtain 0.8 g of yellow gum. This rubber was dissolved in 201 Il of tetrahydrofuran and the solution was mixed with 0.5 liters of lithium aluminum hydride in tetrahydrofuran.
dropwise into a stirred suspension of g. The mixture was heated under reflux for 1 hour, cooled to 0° C. and carefully quenched by addition of 5 d of water. The solvent was removed by evaporation and the residue was extracted with 1QQd of ethyl acetate and 5Qm/ of water.

The ethyl acetate extract was dried and evaporated to give a yellow gummy crude product. Purified by column chromatography on silica gel using ethyl acetate/n-hex/(1:1, vol/vol) as eluent to give (Is)-1',2' as a colorless gum.

3',4'-tetrahydro-37-hydroxy-3'-
(2-hydroxyethyl) S/, S/-dimethoxyspiro [1,3-dithiolane-2,1'-naphthalene)
0.52. I got p.

(Is)-1',2',3',4'-tetrahydro-3'-hydroxy-3'-(2-hydroxyethyl)-5',8'-dimethoxyspiro[1,3-dithiolane-2, 1'-naphthalene] was dissolved in lQm/dry pyridine, and 0.5 g of acetic anhydride was added to this solution. The mixture was left at room temperature for 20 hours, then ice-cold 5M sulfuric acid was poured. The resulting mixture was extracted with ethyl acetate, the extracts were washed with water and sodium bicarbonate solution, dried and evaporated to give (Is)-3'-(
2-acetoxyethyl) -11,, 2/, 3/
, 4/-tetrahydro-3'-hydroxy-S/,S
/-dimethoxyspiro[1,3-dithiolane-2,1'
- Naphthalene:]0.56. ! I got a 9.

(Is)-3'-(2-
acetoxyethyl) -1'+2'+3'+4'-
0.55 g of tetrahydro-3'-hydroxy-5/,S/-dimethoxyspiro[1,3-dithin-2,1'-naphthalene] was added to 5 g of methanol containing 3.5 m of water.
Added to a stirred suspension of 1.65 g of mercuric chloride and 1.65 g of mercuric oxide in 0R1.

After standing for 1 hour at room temperature, the solvent 251117 was removed by evaporation under reduced pressure, 50 t/ml of dichloromethane was added and the resulting suspension was filtered to remove insoluble material. The filtrate was washed three times with Sphagnum 50+j, dried over magnesium sulfate and evaporated to give a solid residue.

Crushed with diethyl ether, melting point 145-148℃
(decomposed) in the form of colorless crystals of (IS)-3-(2-acetoxyethyl)-1,2,3,4-tetrahydro-3-hydroxy-5,8-dimethoxy-1-oxona'phthalene 0.29 g [α)” = +23.9°(c
= 0.05 inch in chloroform).

(Is) -3-(2-acetoxyethyl)-1°2.
0.25μ of 3.4-tetrahydro-3-humano-roxy5-8-dimethoxy-1-oxo-naphthalene was dissolved in 29 mJ of dry tetrahydrofuran, and 200 rng of sodium borohydride was added. The mixture was stirred at room temperature for 2 hours and the solvent was removed by evaporation. Add 25 parts of 10% ammonium chloride and add 2 parts each of ethyl acetate to the mixture.
Extracted three times with 5Wi. The combined ethyl acetate extracts were washed with IJum solution, dried over magnesium sulfate and evaporated to give a clear colorless oil, which was dissolved in 50TR1 of ethyl acetate and dissolved in benzeneboronic acid. 0.125I and 1 drop of acetic acid were added and the resulting solution was heated under reflux for 1 hour. After evaporation of the solvent, the residue was dissolved in toluene.
Dissolve L* in o*. After addition of 25 g of p-)luenesulfonic acid, the solution was stirred at room temperature overnight. The solution was then washed with 10% hydrium bicarbonate solution IQm/, dried and evaporated. The crude product was passed through a column of silica gel 309 with ethyl acetate A//n-hexane (:
(IS)-cis-3-(2-acetoxyethyl)-1 in the form of white crystals with a melting point of 94-95°C.
,2,3,4-tetrahydro-5,8-dimethoxy-1
,3-naphthalenediylbenzeneboronate 0.32
Obtain g; [α]';, = + 52.9° (c =
0.191r in chloroform).

Example 21 (a) (IS)-cis-1,2,3,4,6,11-hexahydro-1,3 in tetrahydrofuran 5011/
,5,12-tetrahydroxy-6,11-dioxo-
3-(p-)lylcarbamoyloxy)methylnaphthacene 0.7! ! A solution of 2+3+6-t! was prepared according to the method described in Example 8(a). ldeoxy-4-0-p-nitrobenzoyl-3-trifluoro aacetamide-α-
L-azibinohexobi7/'/Lukuo Light Z
O, p and silver trifluoromethanesulfonate 1.0.
9. Crude product 6-drideoxy-3-trifluoroacetamido-4-0-p-nitrobenzoyl-α-L-alpinohequinpyranosyl)oxy]-X
, 2,3°4.6,11-hexahydro-3,5,12
-)rihydroxy-6.11-dioquine-3-(p-
Tolylcarbamoyloxy)methylnaphthacene 0.61
,9 was obtained.

(b) 0.61 of the compound obtained according to section (al) was treated according to the method described in Example 1(b) and had a melting point of 21
(1s)-cis-I-[(
2,3,6-trideoxy-3-trifluoroacetamido-α-L-arabinohequinpyranosyl)oxy]
-1,2,3,4,6,11-hexahydro-3,5,
12-trihydroxy-6゜11-dioxo-3-Cp
−)! Jcarbamoyloxy)methylnaphthacene0.
325gl'Jk;[α]"=+273.6°(c=
= 0.05% in dioxane).

(C) Compound obtained according to clause (b) 0.325
．． 9 was treated according to the method described in Example 1 (clK) in the form of an orange-red powder (IS
)-cis-1-[(3-amino-2,3°6-t')deoxy-α-L-arabinohexopyranosyl)oxy)
-1,2,3,4,6,11-hexahydro-3,5,
12-)rihydroxy-6.11-dioxo-3-(p
-1ylcarbamoyloxy)methylnaphthacene hydrochloride 0.319 was obtained; [α]-〇2÷200.2°(c
= 0.049 q6 in methanol).

(IS) used as starting material in section (a)
cis-1,2,3,4,6,11-hexahydro-1,
3,5,12-tetrahydroxy-6,11-dioxo-3-(p-)dylcarbamoyloxy)methylnaphthacene was prepared as follows: 7'7. :m(IS)-cis-1,2,3,4,6,11-hexahuman D-5112
-dihydroxy-3-hydroxymethyl-6,11-dioxo-1,3-naphthacenediylbenzene poronate 1.1 g, p-)dylincyanate) was dissolved in 100 st/d of dry pyridine containing 1.8F. The mixture was heated to 80° C. for 110 minutes and treated according to the method described in Example 1(1) to form a red gum (IS)-cis-1°2.3,4,6.11-hexahydro- 5,12-dihydroxy-6,11-dioxo-3-(p-tolylcarbamoyloxy)methyl-1,3-naphthacenediylbenzene boronate was obtained.

(The compound obtained according to the method described in Section 00 (1) was treated according to the method described in Example 1 (li), with a melting point of 2
(IS)-cis-1,2 in the form of red crystals at 15-218℃
,3,4,6,11-hexahydro-1゜3.5.12
-tetrahydroxy-6,11-dioxo-3-(p-
) dylcarbamoyloxy) methylnaphthacene 0.8g
[α]”=+132.9° (c=(1.05% in dioxane).

Example 22 (a) (Is)-cis-1-[(2,3,6-tIJ
Thioxy-3-trifluoroacetamido-4-〇-methyl-α-L-lyxohexopyranosyl)oxy)-1
,2,3,4,6,11-hexahydro-3,5,12
-trihydroxy-3-hydroxymethyl-6,11-
Dioxonaphthacene 0.4. ! 9 to dichloromethane 750
m1K suspended, trichloroacetyl isocyanate 0
．． 225g was added. This mixture was heated at room temperature under nitrogen for 1
Stir for an hour, then add the resulting clear red solution to 5 Q of water.
ml and evaporated. The resulting red rubber was mixed with 100 Tnl of dichloromethane and 100 ml of methanol.
This solution was treated with 0.1 M aqueous sodium hydroxide to produce a deep purple color. After 3 hours, acetic acid was added to restore the orange color, and the solution was diluted with 50 d of diluted hydrochloric acid, then 5 d of water.
Wash with Qx/7 and dry! 1 and evaporated.

The residue was purified by chromatography on silica gel using ethyl acetate as eluent, mp 152
(IS)-cis-3-(carbamoyloxy)methyl-1-[(2,3,6-drideoxy-3-trifluoroacetamido-4-0-methyl-α-L-) in the form of an orange powder at ~154°C. lyxohexopyranosyl)oxy]-1,
2,3,4゜6.11-hexahydro-3,5,12-
Trihydroxy-6,11-dioxonaphthacene 0.4
I got 15g; 2 [α]. =+169.0°(c=0
．． 049% in dioxane).

(b) Compound 0.39. obtained according to clause (a).
9 was treated according to the method described in Example 9(i) to form an orange-red powder (IS) with a melting point of 194-196°C (decomposed).
-cis-1-[(3-amino-2,3,6-drideoxy-4-0-methyl-α-L-I3xohexobyranosyl)oxy]-3-(carbamoyloxy)methyl-1
,2,3,4,6,11-hexahydro-3,5,11
-Trihydroxy-6°11-dioxonaphthacene hydrochloride 0.3y was obtained; [α]2°=+145.9' (
c=0.049% in methanol).

Example 23 (a) (IS)- in 100d of tetrahydrofuran
cis-1,2,3,4,6,11-hexahydro-1,
A solution of 1.0 I of 3,5,12-tetrahydroxy-6°11-dioxo-3-(phenylcarnocumoyloxy)methylnaphthacene was prepared according to the method described in Example 1(a) to prepare 2,3.6 -) lysooxy-3-trifluoroacetamido-4-0-methyl-α-L-lyxohexopyranosyl chloride and 0.75 g of silver trifluoromethanesulfonate. After purification of the product by chromatography, it was added to 0.215 g of unreacted dioxonaphthacene starting material, mp 137-1
(IS)cis-1-[(2,3,
6-1 Lysooxy-3-trifluoroacetamide-4
-0-Methyl-α-L-liquinhexobyranosyl]oxy)-1,2,3,4.

0.475I of 6.11-hexahydro-3,5,12-)dihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene was obtained; [α)
20=+106.0° (c=o, 051 degrees, in dioxane).

(b) Compound obtained according to clause (a) 0.475
g was dissolved in 1Qm/l of tetrahydrofuran, and this solution was added to an aqueous solution of 0,251 VI hydroxide) and 60 ml of tetrahydrofuran.

The mixture was stirred at room temperature for 45 min, then the solution OpH value was reduced to 0.
．． Adjusted to 8-9 by addition of 2M hydrochloric acid.

This solution was extracted with dichloromethane containing 10% Elnol until the extract was practically colorless.

The combined extracts were washed with water, dried over sodium sulfate without Al and evaporated to give a red gum. This rubber was dissolved in 20 rnl of dichloromethane, filtered and added to P solution.
．． 4d of 165M methanolic hydrogen chloride was added. 200 g of dry diethyl ether was added with stirring to obtain the product as an orange precipitate. After filtration and drying under vacuum, (IS)-cis-1-((3-amino-2,3,6
-trideoxy-4-0-methyl-α-L-IJxohexopyranosyl)oxy]-1,2,3,4°6.11
-hexahydro-3,5,12-)dihydroxy-6,
11-dioxo-3-(phenylcarbamoyloxy)
Obtained 0.355 g of methylnaphthacene hydrochloride; [α:l
,'=+172.3° (c=0.051 coefficient, in methanol).

Example 24 (a) (IS)-cis-1,2,3,4,6,11-hexahydro-1,2 in tetrahydrofuran 70d
A solution of 1.0 g of ,3,12-tetrahydroxy-3-[(0-nitrobenzylcarbamoyloxy)methyl]-6,11-dioxonaphthacene was added to z according to the method described in Example 1(a). , 1.6 g of 3°6-drideoxy-3-trifluoroacetamido-4-0-methyl-α-L-lyxohexopyranosyl chloride and 0.8 g of silver trifluoromethanesulfonate. After purification of the product by chromatography, it is precipitated from dichloromethane solution using n-hexane, melting point 130~
(IS)-cis-[(2,3,
6-drideoxy-3-trifluoroacetamide-4
-0-Methyl-α-L-lyxohexopyranosyl)oxy]-1,2,3゜4.6.11-hexahydro-3,
0.429 of 5,12-trihydroxy-3-((o-nitrobenzylcarbamoyloxy)methyl)-6,11-dioxonaphthacene was obtained; [α:]%'=+138
．． 8° (c=0.05q6 in dioxane).

(b) 0.4 g of the compound obtained according to section (a) was treated according to the method described in Example 23(k)) to give (IS)-cis- 1-[(3-amino-2,3,6-)lysooxy-
4-0-Methyl-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3
,5,12-trihydroxy-3-[(O-nitrobenzylcarbamoyloxy)methyl]-6,11-dioxonaphthacene was obtained; [α]20−+130.8°(c
= 0.051 yen in methanol).

(IS)-cis-1,2,3,4,6,11-hexahydro-3-4(
0-nitrobenzylcarbamoyloxy)methyl]-6
．． 11-Dioxonaphthacene was prepared as follows: (11(IS)-cis-1,2,3,4,6,11-hexahydro-5,12-dihydroxy-3-hydroxymethyl -6,11-dioxo-1,3-nanotacenediylbenzene boronone) 1.0 g 0-nitrobenzyl isocyanate) 1.5. ! Dry pyridine 100 containing i'wo
The mixture was heated to 80° C. for 1.5 hours. (IS)-cis-1,2,3,4,6,11 in the form of an orange gum after treatment according to the method described in Example 1 (il)
-hexahydro-5,12-dihydroxy-3-L: (
0-Nitrobenzylcarbamoyloxy)methyl)-6
, 11-dioxo-1,3-naphthacenediylbenzene boronate was obtained.

The compound obtained according to the method described in Section (11) (,1) was treated according to the method described in Example 1 (IL),
(IS)-cis- in the form of red crystals with a melting point of 123-125°C
1,2,3,4,6,11-hexahydro-1°3.5
．． 1.2 g of 12-tetrahydroxy-3-[(0-nitrobenzylcarbamoyloxy)methyl]-6,11-dioxonaphthacene was obtained; [α]”=+91.1°(
c = 0.05% in dioxane D).

Example 25 (IS)-cis- in (α) tetrahydrofuran 50-
1,2,3,4,6,11-hexahydro-1,3,5
, 12-tetrahydroxy-3=(2-thenylcarbamoyloxy)methyl-6゜11-duoxonaphthacene 0.71, ? The bath solution of 2 t at 6-trideoxy-4 was prepared according to the method described in Example 8(α).
-o-p-nitropenzoyl-3-trifluoroacetamide-α-L-arabinohequinpyranosyl chloride 1 each. It was treated twice with OII and twice with 0.5 g each of silver trifluoromethanesulfonate. After purification of the product by chromatography, (IS)-
cis-1-[(2,3,6-drideoxy-3-trifluoroacetamido-4-o-p-nitrobenzoyl-
α-L-arabinohequinpyranosyl)oxy] ” t
s 2 # 3 $ 416111-hexahydro-
0.56.9 of 3,5,12-trihydroxy-3-(2-thenylcarbamoyloxy)methyl-6,11-duoxynaphthacene was obtained.

(b) 0.56 g of the compound obtained according to (Z)
was treated according to the method described in Example i(b) to give (IS)-cis-1- in the form of orange crystals with a melting point of 212-215°C.
[(2,3,6-drideoxy-3-trifluoroacetamide-α-L-arabinohequinpyranosyl)oxyco-1?2,3,4,6,11-hexahydro-3,5
,12-trihydroxy-3-(2-thenylcarbamoyloxy)methyl-6,11-sooxonaphthacene0
．． 35 g was obtained; [α), g'=+166.2° C
c=0.049% in dioxane).

(C) Compound 0,459 obtained according to the method described in section (b) was treated according to the method described in Example 1 (C) to give (
IS)-cis-1-[(3-amino-2,3゜6-drideoxy-α-L-arabinohequinpyranosyl)oxy] -1* 2 + 3 t 4 s 6 * 11-
hexahydro-3,5,12-trihydroxy-3-(
2-Thenylcarbamoyloxy)methyl-6,11-
Sooxonaphthacene hydrochloride 0.3251″ was obtained; [α
)” = +183.9 @ (6 = 0.05 coefficient, in methanol).

Example 26 (α) (l5)-cis-1,2,3,4,6,11-hexahydro-1,3 in 8Qml of tetrahydrofuran
A solution of 1.3 g of ,5,12-tetrahydroxy-3-(3-thenylcarbamoyloxy)methyl-6111-duoxonaphthacene was prepared according to the method described in Example 8(a) to 2.3.6- )! Jdeoxy-4-0- p-nitropenzoyl-3-trifluoroacetamide-α-
Treated with 1.5 g of L-arabinohexobylanosyl chloride and 5 g of trifluoromethanesulfonic acid (4o, q. After chromatography, in addition to 0.32 g of unreacted dioxonaphthacene starting material, mp 258
(lS)-cis-1-C in orange-red crystalline form at ~259°C
(2s at 6-drideoxy-3-trifluoroacetamido-4-0-p-nitrobenzoyl-α-L
-arabinohequinpyranosyl)oxy]-1,2,3,
4,6sll-Hex Hydro 3゜5 + 12-
) dihydroxy-3-(3-thenylcarbamoyloxy)methyl-6,1t--/oxonaphthacene 0.8
i obtained 8I [(1] fi = -263,4'(
c=0.05% in dioxane).

(6) Compound obtained according to clause (α) 0.67
g according to the method described in Example 1(b) to give (IS)-cis-1- in the form of orange crystals with a melting point of 228-230°C.
((2,3,6-)lysooxy-3-trifluoroacetamido-α-L-arabinohequinpyranosyl)oxy]-1,2,3,4,6,11-hexahydro-3,5
,12-)dihydroxy-3-(3-thenylcarbamoyloxy)methyl-6,11-dioxonaphthacene0
．． 51 g was obtained; [α)20=+197.0° (C=
0.051% in dioxane).

(C) Compound 0,48.9 obtained according to the method described in section (b) was treated according to the method described in Example 1(C) to give a red-orange crystalline powder with a melting point of 198-2006 C (decomposition). (IS)-cis-1-[(3-amino-2
,3,6-dorideoxy-α-L-arabinohequinpyranosyl)oxy], -1*2t3*4s6.11-hexahydro-a,s,12-trihydroxy-3-(3-
0.4 g of chenylcarbamoyloxy)methyl-6,11-dioxonaphthacene hydrochloride was obtained; [α) Affect = +1
917° (c=0.051%, dioxane).

(lS)-cis-It 2 s 3 t' 4-6 * 11-hexahydro-1,3,5,12-tetrahydroxy-3-(
3-Thenylcarbamoyloxy)methyl-6゜11-
Dioxonaphthacene was produced as follows: (1) Drying! 'Thiophene in lysine BOmg-
2.5 g of 3-carboxylic acid was heated to 75°C for 45 minutes to form a mixture of p(1,S)-cis-1,2,
3゜4.6,11-hexadihydro 5,12-dihydroxy-3-hydroxymethyl-6,11-dioxo-
1,3-naphthacene soilbenzene? Ronnay) 1.65
．． ! 9 was added and the mixture was heated to 70° C. for 80 minutes. After processing according to the method described in Example 1(1), (Is)-cis-1°2,a,4. e,tt
-hexahydro-5,11-dihydroxy-3-(3-
chenylcal-cumoyloxy)methyl-6,11-dioxo-1,3-naphthacendylbenzene was obtained from Ronato.

(11) Compound 44t prepared according to the method described in Section (:) Total Example 1 Treated according to the method described in (ii) to give (IS
)-cis-1s 2 * 3 v 4 e 6 ? 1
1-hexahydro-1,3,5-,12-tetrahydroxy-3-(3-thenylcarbamoyloxy)methyl-6°11-dioxonaphthacene 1.56.9 was obtained;
[α] = + 118.8 @ (C = 0.049 chi, in dioxane).

Example 27 (α) Tetrahydrofuran 9QmA! Inside (IS)-
cis-1*2s3*4t6tll-hexahydro-1,
A solution of 1.3y of 3,5,12-tetrahydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene was added to 213,6-117deoxy- 3-Trifluoroacetamido-4-〇-methyl-α-L-arabinohexobyranosyl chloride 0.91! and trifluoromethanesulfone e410.65I. The product was purified by column chromatography and then added to 0.63.9% of the unreacted dioxonaphthacene starting material in the form of orange crystals with a temperature of 243-244°C (lS).
-cis-1-[(2,3,6-)lysooxy-3-trifluoroacetamido-4-0-methyl-α-L-arabinohexopyranosyl)oxy]-1*2*3s4.6
, 11-hexahydro-3,5,12-1'lihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene o, 72I was obtained; [α]"
=+150.9° (c=o, coefficient 05, in dioxane).

(6) Compound obtained according to clause (α) 0.61!
was treated according to the method described in Example 23(b) to give (IS)- in the form of an orange powder with a melting point of 212-214°C (decomposed).
cis-1-((3-amino-2t a t e -) lysooxy-4-0-methyl-α-L-arabinohexopyranosyl)oxy] -i l 21 at 4v
0.391 of 6+11-hexahydro-3,5,12-)dihydroxy-6,11-sooxo-3-(phenylcarbamoyloxy)methylnaphthacene hydrochloride was obtained; [
α), 7=+204.0” (c=o, o s ratio, in methanol).

Example 28 (a) (lS)-cis-1+2t3,416@11-hexahite a-1t3 in tetrahydrofuran 90d
, 5.12-tetrahydroxy-6゜1x-yoxo-
A solution of 1.2 g of 3-(phenylcarbamoyloxy)methylnaphthacene was prepared according to the method described in Example 1(α) to form 2,3.6-)lysooxy-4-o-ethyl-3-
It was treated with 0.9 g of trifluoroacetamide-α-L-lyxohexopyranosyl chloride and 0.6 g of silver trifluoromethanesulfonate. After purification of the product by column chromatography, it was added to 0.6.9% of unreacted dioxonaphthacene starting material, mp 138-14
(IS)-cis-1-((2,
3,6-)lysooxy-4-O-ethyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl)
oxy)-1s2e3.4,6,11-hexahydro-
3s 5 t 0.9 g of 12-trihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene was obtained;
= 0.05% in dioxane).

(b) Compound 0°73. obtained according to clause (α).
9 was carried out according to the method described in 23 (6), and was obtained in the form of an orange powder (IS) with a melting point of 178-180°G (decomposition).
-cis-1-((3-amino-2,3,6-drideoxy-4-Q-ethyl-α-L-lyxohexopyranosyl)oxy)-1+2*3*4t6y11-hexahydro-3,,5 , 0.45 g of 12-trihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene hydrochloride was obtained; [α] = + 131.
5” (6=0.05, in methanol).

2,3,6-Drideoxy-4-0-ethyl-3-trifluoroacetamide-α-L-lyxohexopyranosylchloride V used as the starting material in Section (α) was prepared as follows. (1) Methyl 3-acetamide-21316-1 lysooxy-β-L-lyxohexopyranoside 5.0.9 was added in the dark to 20 g of trimethylformamide containing 25+ ILl of ethyl iodide and 1(l) of silver oxide. The mixture was heated to 45 °C in the mixture. After 17 hours, the mixture was filtered through Celite and the lachrymal fluid was evaporated. The resulting gum was purified by column chromatography, with a /','tli point of 199-200 °C. Methyl 3-acetamido-2,3,6-drideoxy-4-0-ethyl-β-L-lyxohexopyranoside 3 in the form of colorless crystals
．． 411 was obtained; [α]ge=-75.0'' (C=0.5
% in methanol).

(ii) 3.0 g of the compound obtained according to clause (1)
Dissolve JQ in 53 ml of water containing 10.5 g of barium hydroxide.
'(did.

The mixture was heated under reflux for 20 hours and cooled.

Next, it was diluted with 100M water. Carbon dioxide was bubbled through the mixture for 1 hour, and after filtration, liquid F was evaporated to give a white solid, which was dried over potassium hydroxide at 50°C. The dried product was suspended in dry diethyl ether 80117 and cooled to 0°C while trifluoroacetic anhydride 1O
N was added dropwise. The resulting mixture was stirred at room temperature for 18 hours,
Filter and evaporate to give a white crystalline solid. Disintegrated with a mixture of diethyl ether/n-hexane, melting point 18
1.4 g of methyl 2,3.6-)lysooxy-4-0-ethyl-3-trifluoroacetamide-β-L-lyxohexopyranoside was obtained in the form of colorless crystals at 3-185°C;
[α] Sweet -88.3° (c = 0.49 degrees, in methanol).

(iii) Compound 1 obtained according to clause (ii).
4 g was suspended in a 20% (vol/vol) mixture of acetic acid and water 38- and heated under reflux for 3 hours. The solvent was removed by evaporation and the residue was purified by column chromatography to give 2 as colorless crystals with a melting point of 183-184°C.
．． 3.6-Drideoxy-4-0-ethyl-3-trifluoroacetamide-L-lyxohexopyranoside1.
2.9 was obtained; [α:I'=-175.4°((!=0
．． 5ch in methanol).

Gv) Compound 0.8 obtained according to clause (iii)
Ii was dissolved in pyridine 16.5- at 0°C, stirred, and p-nitrobenzoyl chloride 0.81! added. This mixture was stored at 0°C for 18 hours and then heated in ice water for 20 hours.
I poured it into 0J. After 30 minutes, the product was extracted three times with 50 ml of dichloromethane each, and the combined extracts were extracted with 1011 ml of dichloromethane.
CQ9 2 times with 50 penalties each, 59 m of saturated sodium chloride solution
twice with 59 m/e % saturated sodium bicarbonate solution and finally 5 ml of saturated sodium chloride solution (washed with IIJ. anhydrous sulfuric acid) after drying over IJum.

The solvent I8 was removed by evaporation, and p-nitropenzoyl 2,3°6-drideoxy-4-0-ethyl-3-trifluoroacetamide-α-L-lyxohexopi was obtained in the form of colorless crystals with a melting point of 148-150°C. 0.96 g of ranoside was obtained ((+=0.3 qb, in methanol).

(v) Compound obtained according to clause (iv) 0.91
was dissolved in 40 g of dichloromethane at 0°C, and hydrogen chloride was bubbled into this solution for 10 minutes at 0°C. The mixture was then stirred at room temperature for 15 minutes and the solution was removed by evaporation. The residue was stirred for 10 minutes with 20 liters of dichloromethane and filtered. Evaporate P solution to obtain crude 2*3t
0.9 g of 6-drideoxy-4-0-ethyl-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride was obtained, which was used directly in the reaction described in section (α).

Example 29 (IS)-cis-1,2,3,4,6.11-hexahydro-1,3, in (α) tetrahydrofuran 100-
5,12-tetrahydroxy-6゜11-dioxo-3
-(phenylcarpamoyloxy)methylnaphthacene 1
．． A solution of 45.9 was prepared as 4-O-pentrue 2,a,6=hlysooxy-3 according to the method described in Example 1(a).
-Trifluoroacetamide-α-L-lyxohexopyranosyl chloride 1.0! ? and treated with trifluoromethanesulfone 0.611 g. After the product was purified by column chromatography, 0.63.9% of the unreacted sooxonaphthacene starting material was added to n-
Precipitation from dichloromethane solution with hexane gives (lS)-cis 1 as an orange powder with a melting point of 123-127°C.
-((4-0-benzyl-2,3,6-drideoxy-3-trifluoroacetamido-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro- 3゜5.12-trihydroxy-6,11
-0.77 g of -sooxo-3-(phenylcarbamoyloxy)methylnaphthacene was obtained; [α)'=+67.3
@(C=0.052, in dioxane).

(6) Dissolve 0.61 of the compound obtained according to section (α) in 25 tnl of tetrahydrofuran, and add this solution to 0.
．． Added to 60 g of 5M aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 45 minutes and the pli value of the solution was then adjusted to 0.5.
Adjusted to 8-9 by addition of M hydrochloric acid. This solution,
It was extracted repeatedly with dichloromethane until the extract was practically colorless. The combined extracts were washed with water and dried over anhydrous sodium sulfate.

Evaporation gave a red gum. This rubber was dissolved in dichloromethane j20+u and filtered, and 4.5 ml of 0.16AI methanolic hydrogen chloride was added to the P solution. Next, 20ON of dry diethyl ether was added with stirring to obtain a product in the form of an orange precipitate. After filtration and drying under vacuum, (I
S)-cis-1-[(3-amino-4-0-benzo-2.3.6-)lysooxy-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6, 0.45 g of 11-hexahydro-3t5,12-)dihydroxy-6,11-duoxo-3-(phenylcarbamoyloxy)methylnaphthacene hydrochloride was obtained; [α] = +61.
3@(C=Q, 951% in methanol).

The 4-o-pentrue 2 $ a * s -trideoxy-3-trifluoroacetamide-α-L-lyxohexopyranosyl chloride used as the starting material in Section (α) was prepared as follows. ) Methyl 3-acetamido-2,3,6-)lysooxy-β-L
5.011 lyxohexopyranoside was dissolved in a mixture of 3.2 kg of pennorbromide containing 75 g of completely dry trimethylformamide and 15 g of silver oxide. The mixture was stirred in the dark for 72 hours, filtered and the P solution was evaporated to give a crystalline mixture of product and unreacted starting material. Separate the products by column chromatography.

Methyl 4-O-benzyl-2*3@6-)lysooxy-3-trifluoroacetamide-β-L-lyxohexopyranoside 2.1 in the form of colorless crystals with a melting point of 159-160°C.
．． 9 was obtained; [α] = -89,2° (c = 0..5%
, in methanol).

(ii) 2.5 g of the compound obtained according to clause (α)
was dissolved in 15 ml of ethanol and the resulting solution was added to a stirred mixture of barium hydroxide 1&5I and 85 ml of water. This mixture was heated under reflux for 4 days.

It was cooled and diluted with 15011 L of water. The mixture was bubbled with carbon dioxide for 1 hour, and after filtration, the P liquid was evaporated to give a residue, which was dried over phosphorus pentoxide at 70°C. The dried residue was diluted with 75 d of anhydrous diethyl ether at 0°C.
Suspend the trifluoroacetic anhydride IQ with stirring.
m/ was added dropwise. The resulting mixture was stirred in one portion at room temperature, filtered, and the P solution was evaporated to give a white residue, which was purified by column chromatography. Melting point 17
Methyl 4-Q-benzyl- in the form of colorless crystals at 6-177℃
247 g of 2,3,6-drideoxy-3-trifluoroacetamide-β-L-lyxohexopyranoside were obtained.

(iii) Compounds obtained according to clause (ii) 2.
05,! i' in acetic acid and 20% water (vol/υor
) of the mixture and the resulting mixture was refluxed for 2 hours.
．． Heated for 5 hours.

The solvent was removed by distillation and the residue was triturated with n-hexane to give 4-0-
Benzyl-2,3,6-)lysooxy-3-trifluoroacetamide-L-lyxohexopyranoside 1.5g
[α] = -16&5° (c = 0.5 coefficient, in methanol).

(iv) Section (in) IIC Compound 1 thus obtained
．． 5I was dissolved in 25 m of pyridine at 0°C and 1.22.9 m of p-=trobenzoyl chloride was added while stirring. This mixture was stored at 0°C for 18 hours, then heated to 400°C in ice water.
I poured it into the go. After 0.5 hours, the product was extracted 3 times with 100 g each of dichloromethane, and the combined extract was extracted twice with 100 g each of 100 sulfuric acid, and 100 i+ξ of saturated sodium chloride solution.
Washed twice with 100 m each of saturated sodium bicarbonate solution and finally with 100 m of saturated sodium bicarbonate solution. After drying, the solvent was removed by evaporation, melting point 132-1
Colorless crystalline p-
Nitrobenzoyl-4-0-benzyl-2,3,6-)
1.7 g of lysooxy-3-trifluoroacetamide-L-lyxohexopyranoside was obtained; [α] bamboo = -12
6° (C=0.5 factor, in methanol).

(v) 1.0 g of the compound obtained according to section Gv)
was dissolved in 49M1 of sochloromethane at o'c, and hydrogen chloride was bubbled into this solution at 0°C for 10 minutes. The mixture was then stirred at room temperature for 15 minutes and the solvent was removed by evaporation. In the evening the residue was stirred with 20 ml of sochloromethane for 10 minutes and filtered. Evaporate the filtrate to obtain crude 4-0-
Benzyl-“2 t 3 + 6-Drideo! Sea 3
-) Lifluoroacetamide-α-L-lyxohexobyranosylchlorite”1.Ol was obtained, which was used directly in the reaction described in section (α).

Example 30 (α) (IS)-cis-1- in 10 ml of dry pyridine
[(2,3,6-tetradeoxy-3-trifluoroacetamido-α-L-threohexopyranosyl)oxy]-i, 2,3,4,6.11-hexahydro-3,5
, 12-trihydroxy-3-hydroxymethyl-6,
11-dioxonaphthacene 0.6.9 and butane-1,
4-diisocyanate) 70! The ay mixture was left at room temperature for 3 weeks.

The solvent was then removed by evaporation and the residue was purified by chromatography to give 3.3'-[tetramethylenebis(carbamoylmethylene)]bis-1- [(2,3,
4,6-tetradeoxy-3-trifluoroacetamido-α-L-threohexopyranosyl)oxy:)-i
t2t4*6t11-hexahydro-3,5,12-)
Dihydroxy-6,11-sooxonaphthacene 364■
obtained; [α]=+196.1' (c=0.049
%.

in dioxane).

(b) Compounds o, s obtained according to clause (α)
21 was treated according to the method described in Example 9(b) to give 3.3'
-[tetramethylenebis(carbamoyloxymethylene)]-]bis-IS)-cis-[(3-amino-2゜3
．． 4.6-titradeoxy-α-L-threohequinpyranosyl)oxy]-1*2t3t4+6s11-hexahydro-315112-trihydroxy-6,11-sooxonaphthacene dihydrochloride 0.42.9 was obtained ; [α]
C=+274.9° (C=0, θ51qb, in methanol).

Example 31 (a) (IS)-cis-3-(4-chlorophenylcarbamoyloxy)methyl-1t2t3t4 in 100 d of tetrahydrofuran and 7 mAt of dimethylformamide
+6tll-hexahydro-1゜3.5.12-tetrahydroxy-6,11-dioxonaphthacene 1.1.9
A solution of %2e was prepared according to the method described in Example 2(a).
316-IJdeoxy-4-o-p-nitropensoyl-3-IJ7k,It.

Acetamide-α-L-arabinohequin pyranosyl chloride 1.0g and silver trifluoromethanesulfonate 0
．． 5.9. After crystallization, melting point 267-268℃
(IS)-cis-3-(4-10lophenylcarpamoyloxy)methyl-1-[(2,3,6
-Drideoxy-3-trifluoroacetamide-4-
0-p-nitropenzoyl-α-L-arabinohequinpyranosyl)oxy]-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-
0.96 g of dioxonaphthacene was obtained.

(6) 0.8 g of the compound obtained according to section (a) was treated according to the method described in Example 1(b) to give a melting point of 20
(IS)-cis-3-(4
-10Lofenyl(lupamoyloxy)methyl-1-[
(2,3,6-)lysooxy-3-trifluoroacetamido-α-L-arabinohequinpyranosyl)oxy]
-1t213t4t6t11-hexahydro-3,5,
12-) Dihydroxy-6,11-duoxonaf, Tacene 0.53.9 was obtained. [α)”=+175.8°(C
=0.05%.

in dioxane).

(C) Compound obtained according to clause (b) 0.49.
9 was treated according to the method described in Example 1(C) to give (IS) in the form of an orange-red powder with a melting point of 183-187°C (decomposition).
-cis-1-((3-amino-2,3,6-drideoxy-α-L-arabinohequinpyranosyl)oxy)-3
-(4-chlorophenylcarbamoyloxy)methyl-
1,2,3,4,6,11-hexahydro-3,5,1
0.46 g of 2-trihydroxy-6,11-dioxonaphthacene hydrochloride was [:(!]5=+192.
．． 4° (c=0.051%.

in methanol).

Example 32 (α) (l5)-cis-3-(trichloroacetylcarbamoyloxy)methyl-t, 2,3.4m6.11-hexahydro-1t in 60mt of tetrahydrofuran
3 t 5 t 12-tetradodroxy-6,11-
A solution of 1.0511 dioxonaphthacene was prepared in Example 8 (
2,3,6-dolideoxy-4-o-p-nitrobenzoyl-3-trifluoroacetamide-α-L-arabinohequinpyranosyl chloride according to the method described in α) 1.51! and silver trifluoromethanesulfonate 0.
5I! Processed with.

After purification by chromatography, the crude (IS)-cis-3-()+7chloroacetylcarpamoyloxy)methyl-1-[(2+ a
s 6-drideoxy-3-trifluoroacetamido-4-o-p-nitrobenzoyl-α-L-arabinohequinpyranosyl)oxy]-1s2.3,416.11
-hexahydro-3,5゜12-trihydroxy-e,
xt-xoxonaphthacene was obtained.

(6) The compound obtained according to section (α) was dissolved in a mixture of 75 ml of dichloromethane and 75 ml of methanol and a 0.5 M hydroxide solution was added to give a deep purple color. After 3Fi=i, the color returned to orange by adding acetic acid. Dilute the mixture by adding 300 d of water,
The product was extracted three times with 1,001,117 dichloromethane each. The combined extracts were converted into a furnace over anhydrous sulfuric acid and evaporated to give a red residue. Crystallized from ethyl acetate, orange-red Ma-like f (I
S)-cis-3-(carbamoyloxy)methyl-1
-[(2,3,6-drideoxy-3-trifluoroacetamide-α-L-arabinohequinpyranosyl)oxy:l-1,2゜3.4,6,11-hexahydro-a
, s, 12-trihydroxy-6,11-dioxonaphthacene 0.46 & was obtained; [α] = +197.1°
(C=0.5% in dioxane) (C) 0.5 g of the compound obtained according to section (b)
was treated according to the method described in Example 1(c) to give an orange colored powder (1s) with a melting point of 184°C to 180°C (decomposition).
-cis-1-((3-amino-2va*6-trideoxy-α-L-arabinohequinpyranosyl)oxy]-3-(carbamoyloxy)methyl-1°213
．． 4,6.11-hexahydro-3,5゜12-trihydroxy-6,11-sooxonaphthacene hydrochloride 0.3
Obtained 711; [α] Town cry 216.7° (C engineering 0.51
% in methanol) (1s)-cis-3-()IJ dichloroacetylcarbamoyloxy)methyl-i*2*a used as starting material in section (α), 4. s,it-hexahydro-11
3,5,12-tetrahydroxy-6,11-dioxonaphthacene was produced as follows.
6 ell-hexahydro-5,12-dihydroxydi-3-hydroxymethyl-6,11-dioxo-1,
3-Naphthacenediylbenzene poronate 1,0.9
It was suspended in 200 d of dichloromethane, and 0.5 g of trichloroacetyl isocyanate was added.

After stirring for 1 hour in one chamber, a clear red solution was obtained. The solvent was removed by evaporation and the residue was dissolved in dichloromethane 1
5m, 2-methyl-2,4-bentanediol 15me
and 3 tnl of acetic acid.

The resulting mixture was allowed to stand at room temperature overnight. Next, this solution was diluted with 100 ml of chloromethane and washed four times with 75 grams of sphagnum moss. After drying over anhydrous sodium sulfate, the solvent was removed by evaporation and the residue was triturated with a mixture of ethyl acetate and diethyl ether to 1M! II points 125-128
(IS)-cis-3-(trichloroacetylcarbamoyloxy)methyl-i,2,3,4,6 as a red powder at ℃
, 11-hexahydro-1,3,5,12-tetrahydroxy-6,11-dioxonaphthacene 1.1 g was obtained; [α]' = +91.9° (Co, o s /, sooxane During).

Example 33 (α) (1,S')- in tetrahydrofuran 60p
cis-' + 2 * 3 * 4 ' + 6 t 1
1-hexahydro-1,315,12-tetrahydroxy-6゜11-duoxo3-[1(,S')-(phenylcarbamoyloxy)ethyl]naphthacene 0.86
g solution according to the method described in Example 19(α),
2゜3.6-Drideoxy-4-op-nitrobenzoyl-3-trifluoroacetamide-α-L-arabinohequinpyranosyl chloride 1. 0.5 g of trifluoromethanesulfonic acid scissors. The crude product was crystallized from ethyl acetate/diethyl ether as (IS)-cis-1 in the form of orange crystals, mp 278-282°C.
-((213,6-trideoxy-3-trifluoroacetamide-4-o-p-nitropenzoyl α-L-
arabinohexopyranosyl)oxy) -1t 2 e
3 t 4 *6111-hegi thi)-”0-315
．． 12-) Lysooxy-6,11-dioxo-3-[1
0.6 g of (S)-(phenylcarbamoyloxy)ethyl]naphthacene was obtained.

(b) Compound o obtained according to clause ((IL),
5G 511 was treated according to the method described in Example i(b) to give (l5)- in orange crystals with a melting point of 266-267°C.
cis-1-((2,3,6-1-lysooxy-3-trifluoroacetamido-α-L-arabinohexobyranosyl)oxy] -1,21a s 4 s e t
i 1-hexavitro-3,5,12-)lihydroxy-6.11-dioxo-3-[1(S)-(phenylcarbamoyloxy)ethyl]naphthacene 0,45.9 was given; [α), '=+131.26 Cc=0.05
% in dioxane).

(C) Compound 0.42. obtained according to clause (b).
1i+ was treated according to the method described in Example t9(c) to give (1
s)-cis-1-(”(3-amino-2,3,6-drideoxy-α-L-arabinohexobyranosyl)oxy]-1,2,3f4,6.11-hexahydro-3*5
y12-trihydroxy-6,11-dioxo-3-[
1(,S')-phenylcarbamoyloxy)ethyl]
Naftacene hydrochloride 0.351! Obtained + [a]”=+
179.8° ((!=0.051, in methanol) (1.S') used as starting material in section (α)
-cis-”y2t3*4*6+11-hexahitday-t
, a, s, 12-tetrahydroxy-6゜11-dioxo-5-(x(s)-(phenylcarbamoyloxy)
Ethyl]naphthacene was prepared as follows: (1) Following the method described in Example 1B(1), (IS)
-sisu1.2,3,4,6.11-hexahylow5
1.0 g of 112--/hydroxy-a-[1(S)-(hydroxy)ethyl]-6,11-dioxo-1,3-naphthacenediylbenzene poronate was treated with 1.5 g of phenyl isocyanate). .

Red rubbery crude (IS)-cis-1,2,3,-4
,6,11-hexahydro-5,12-dihydroxy-
6,11-Sooxo a-[t(S)-(phenylcarbamoyloxy 3-naphthacenesoylbenzene) was obtained as ronate, which was used without further preparation.

(ii) Ni (1) IC Therefore, the obtained benzene yl? Ronate was treated according to the method described in Example 1B(ii) and was prepared in the form of a red powder with a melting point of 155-160°C (
IS)-cis-l, 2, 3t4*6
#1 1-hexahydro-1.

3,5.12-tetrahydroxy-6,11-dioxo-3-[1(S')-(phenylcarbamoyloxy)
Obtained 0.925 g of ethyl naphthacene; to [α]=+
61.9° (c=0.05%.dioxane).

(IS)-cis-1, 2 t a e 4 * 6 y 1 1- used as the starting material in Section (1)
Hexahydro-5.12-Nhi)'Ro*C3-[1(
s)-(hydroxy)ethyl]-6,11-dioxo-
1,3-Naphthacenediylbenzene poronate was prepared as follows.(1s)-cis-
341(S)-(acetoxy)ethyl]- 1 t 2
t'a* 4-tetrahydro-5,8-dimethoxy-1,3-naphthacenesoylbenzene converts ronate to the corresponding (IS)-cis-3-(1(A')-(acetoxy)ethylcou isomer (IS)-cis-3-(1(,5)-(acetoxy)ethyl)-1,2* as yellow crystals with a melting point of 172-174°C. 3,4.s, 12-hexahydro-5°12-dioxo-1,3-naphthaceneduylbenzene is ronate; [α]ge=+98.7° (C=
(IS)-cis-5,12-diacetoxy-3-[11)-(acetoxy)ethyl]-1y2*3゜4-tetrahydro- as pale yellow crystals with a melting point of 238-240°C 1,
3-naphthacenzylbenzene boronate + (α);
=+20112° (C= O, OS, chloroform)! (IS)-cis-5,12-duacetoxy-3-[1(S)-Cacetoxy)ethyl]-1y2t3t4.6,11-hexahydro-6,11-dioxo- as pale yellow crystals with a melting point of 178-180°C. 1,3-naphthacenediylbenzene boronate; [α)”=+146.6°
((!=0.05%, in lyloloform); and (IS)-cis-1,2s3s4t6+11-hexahydro-5,12 as red crystals with a melting point of 224-226°C.
-dihydroxy-3-[1(S)-(hydroxy)ethyl]-6.11-dioxo-1,3-naphthacenzylbenzene boronate; [α]=+269.9° (6=
0.05%% in dioxane].

Example 34 (α) (IS)-cis- in 37m tetrahydrofuran
1,2,3,4s6,11-hexahydro-t, 3. s
, 12-tetrahydroxy-6゜11-dioxo-3-
[1(/?)-(phenylcarbamoyloxy)ethyl]naphthacene 2201! A solution of Ig was stirred at -6°C under a nitrogen atmosphere and 2.3.
6-drideoxy-3-trifluoroacetamide-4
A solution of -o-methyl-α-L-lyxohexopyranosyl chloride 155q and fluoromethanesulfone li silver 2061Fl & 1 in diethyl ether 1Qmj
Added simultaneously over 0 minutes. After stirring the mixture for a further 2 hours at -5° C., the mixture was further added with 77 ml of the above chlorosugar in 3 ml of tetrahydrofuran and 10 3 ml of silver trifluoromethanesulfonate in 5 ml of soethyl ether.
fff was added over 8 minutes. The mixture was stirred for an additional 110 minutes at -7°C and then poured into a mixture of 10% potassium bicarbonate solution 1651R1 and 15ml of ethyl acetate. This γ mixture was filtered, and the P solution was transferred to a separating funnel to separate one layer.

The organic layer was washed twice with 250 ml of sphagnum moss, dried over anhydrous magnesium sulphate and evaporated. The residue was passed through a column of Silica Dull 40.9 using ethyl acetate 740 as the eluent.
Chromatographed using ~60°C petroleum ether (113°υol/vol).

(IS)-cis-1-((213,6-)lysooxy-
3-Trifluoroacetamide-4-Q~methyl-α-
L-lyxohexopyranosyl)oxy] -1,21"
I 4? 6111-hexahydro-3,5,12
-trihydroxy-6,11-dioxo-3-[1(R
)-(phenylcarbamoyloxy)ethyl]naphthacene 3osmy was obtained.C,h- This was used without further purification.

(6) A solution of compound 117~ obtained according to section (α) in 1 ml of tetrahydrofuran was added to 0.1 M sodium hydroxide solution 37- and this dark purple mixture was stirred at room temperature under nitrogen for 4 hours. . The solution was brought to a pB value of 8 by the addition of 5M hydrochloric acid and the mixture was extracted 4 times with 2011/ml of dichloromethane.

The combined extracts were washed with water, dried over anhydrous sodium sulfate, and evaporated. Dichloromethane 1π of the residue
Dissolved in 0.25 g of AI methanolic chloride O,
9 tni and then 45 m/m of diethyl ether were added. This mixture was left at 0°C overnight. The product was separated and dried under vacuum to give (IS)-cis-1-[(3-amino-2,3,6-
Dorideoxy-4-O-methyl-α-L-lyxohexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11
-SooΦSo3-[1(R)-(phenylcarbamoyloxy)ethyl]naphthacene hydrochloride 31F/9 was obtained;
[α]:=+101°(c=o, 051Ji.

in dioxane).

Claims (1)

[Claims] 1. In the general formula, R is a hydrogen atom, lower alkyl, aryl or aryl-(lower alkyl) group, or a 5- or 6-membered heteroaromatic whose heteroatom is nitrogen, oxygen or sulfur. group group or formula % formula % () n' represents hydroxy, lower alkoxy, amino, lower alkylamino, di(lower alkyl)amine or arylamino group, n represents an integer from 1 to 4, n' is 2 represents an integer of ~10, each of R1 and R11 represents a hydrogen atom, or R
One of 1 and R2 represents a hydrogen atom, and the other represents a hydroxy, lower alkoxy or benzyloxy group, and X is of formula CH. -CH,-, -CH- or -〇H2-CH,-(i)
(ii) A compound represented by the group (iii) and a pharmaceutically acceptable acid addition salt thereof. 2, R is lower alkyl, aryl or aryl-(
lower alkyl) group, a 5- or 6-membered heteroaromatic group in which the heteroatom is nitrogen, oxygen or sulfur or a group of the formula (
A compound according to claim 1, wherein R1 and R2 each represent a hydrogen atom, or one of R1 and R2 represents a hydrogen atom and the other represents a hydroxy or methoxy group. 3. The compound according to claim 2, wherein R represents an aryl group. 4.No? 4. A compound according to claim 3, wherein represents phenyl. 5. The compound according to claim 3, paragraph 3 or 4, wherein one of R1 and R1 represents a hydrogen atom and the other represents a hydroxy group. 6. The compound according to any one of claims 2 to 5, wherein X represents a group of formula (1) or (11) according to claim 1. 7, (tH)-cis-[(3-amino-2,3°6-drideoxy-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3 ,5
, 12-trihydroxy-6°. 8, (IS)-cis-1-[(3-amitous 3.6-
Dorideoxy-α-L-arabinohexobyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3
,5,12-trihydroxy-6,11-dioxo-3
-(Phenylcarbamoyloxy)methylnaphthacene and a pharmaceutically acceptable acid addition salt thereof. 9, (IS)-cis-t-[(a-amytose3.6-
) lysooxy-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,
5,12-trihydroxy-6,11-dioxy-3-
(1(7?)-(Phenylcarbamoyl)ethylfunaftacene and hisono The compound according to claim 1, which is a pharmaceutically acceptable acid addition salt. 10, (IS)-cis-t- (:(a-amino-2,3
,6-drideoxy-α-L-arabinohexobyranosyl)oxy)-1,2,s,4,6゜11-hexahydro-3,5,12-)rihydroxy-6,11
-Dioxo-3-[1'(7?l(phenylcarbamoyloxy)ethyl)naphthacene and a pharmaceutically acceptable acid addition salt thereof. 11. (IS) -cis-x-((a-amino-2,3,
6-) Lysooxy-α-L-lyxohexopyranosyl)
oxy)-3-(4-chlorophenylcarbamoyloxy)methyl-1,2,3゜4.6.11-hexahydro-3,5,12-)dihydroxy-6,11-dioxonaphthacene, (IS)- cis-1-((3-amino-2
, 3゜6-drideoxy-α-L-lyxohexopyranosyl)oxy) -1, 2, 3, 4', 6, 11-
hexahydro-3,5,12-)lihydroxy-3-(
4-nitrophenylcarbamoyloxy)methyl-6,
11-Dioxonaphthacene, (IS)-cis-1-[(
3-Amino-2,3゜6-drideoxy-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,
11-hexahydro-3,5,12-)lihydroxy-
3-(4-methoxyphenylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-cis-
1-((3-amino-2,3゜6-drideoxy-α-
L-lyquinhequinpyranosyl)oxy)-1,2,3,
4,6,11-hexahydro-3,5,12-trihydroxy-3-(3-hydroxyphenylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS
)-cis-1-1: (a-amino-2,3゜6-drideoxy-α-L-lyxohexopinocyl)oxy)-
1,2,3,4,6,11-hexahydro-3,5,1
2-Trihydroxy-3-(methylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-cis-1-[:(3-amino-2,3゜6-
Dorideoxy-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,
5,12-)lihydroxy-3-(2-thenylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-7su-t-((a-amino-2,3+4.6
-titradeoxy-α-L-threohexopyranosyl)
(oxy)-1,2,3,4,6,11-hexahydro-
3,5,12-)lihydroxy-6,11-dioxo-
3-(phenylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-((a-amino-2,3゜4,
6-Titrateoxy-α-L-threohequinpyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,5,12-)dihydroxy-6,11-dioxo-3-(3 -pyridylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-((3-amino-2,3
゜6-Drideoxy-4-0-methyl-α-L-lyxohexopyranosyl)oxy)-3-(benzylcarbamoyloxy)methyl-1,2,3,4゜6.11-hexahydro-3, 5,12-trihydroxy-6,11-
Dioxonaphthacene, (lS)-cis-1-((3-amino-2,3°6-drideoxy-α-L-lyxohexopyranosyl)oxy)-3-((2-carboxyethyl)carbamoyl Oxycomethyl-1,2,3,4゜6
．． 11-hexahydro-3,5,12-trihydroxy-6,11-dioxonaphthacene, (IS)-cis-1
-((a-amino-2,3゜6-drideoxy-α-L
-lyxohexopyranosyl)oxy)-1,2,3,4
,6,11-hexahydro-3,5,12-)lihydroxy-3-((2-(methoxycarbonyl)ethyl]carbamoyloxy]methyl-6,11-dioxonaphthacene, (IS)-cis-1 -((a-amino-2,3°6-drideoxy-α-L-lyxohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,5
, 12-trihydroxy-6゜11-dioxo-3-1
:(2-(Propylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene, (IS)-cis-1-((3-amino-2,3°6-drideoxy-α-L-arabinohexobyranosyl)oxy)- 1,2,3,4,6,11-hexahydro-3,
5,12-)lihydroxy-6,11-dioxo-3-
[[2-(Propylcarbamoyl)ethyl]carbamoyloxy]methylnaphthacene, (IS)-cis-1-[:(3-amino-2,3゜6-
Dorideoxy-4-0-methyl-α-L-lyxohexopyranosyl)oxy] -1,,2,a. 4, 6, 11 +, hexahydro 3.5.12-
) dihydroxy-6-11-dioxo-3-[:2-(
A compound according to claim 1 selected from phenylcarbamoyloxy)ethylnaphthacene and pharmaceutically acceptable acid addition salts thereof. IZ (xS)-cis-t-((a-7minose3.
6-Drideoxy-α-L-arabinohequinpyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-3-(p- Tolylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-((3-amino-2,3゜6-drideoxy-4-〇-methyl-α-L-lyxohexopyranosyl)oxy)-3- (carbamoyloxy)methyl-1,2,3,4,6,11-hexahydro-3,5
,12-)dihydroxy-6,11-dioxonaphthacene, (IS)-cis-t-((a-amino-2,λ6-dolideoxy-4-0-methyl-α-L-lyxohexopyranosyl )oxy)-1,2,3°4.6.11-hexahydro-3,5,12-)dihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene, (IS)-cis -1-[(3-amino-2,
3゜6-dolideoxy-4-0-methyl-α-L-lyxohexinpyranosyl)oxy)-1,2+3+4.6.
11-hexahydro-3,5,12-trihydroxy-
3-((o-nitrobenzylcarbamoyloxy)methyl)-6,11-dioquinaphthacene, (IS)-cis-1-((3-amino-2,3°6-drideoxy-α-L-arabino hequinpyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3,
5,12-)lihydroxy-3-(2-thenylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-cis-1-(:(3-amino-2,3°6-
Dorideoxy-α-L-arabinohequinpyranosyl)oxy)-1,2,3,4,6,11-hexahydro-a
, s, 12-)lihydroxy-a-(a-thenylcarbamoyloxy)methyl-6,11-dioxonaphthacene, (IS)-cis-t-((a-amino-2,3°6-drydeoxy-4 -0-Methyl-α-L-acypinohexopyranosyl)oxy)-1+2+&4.6.11-hexahydro-3,5,12-)dihydroxy-6,11-
Dioxo-3-(phenylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-((3-amino-2
,3゜6-drideoxy-4-0-ethyl-α-L-lyxohexopyranosyl)oxy)-1,2,3゜4.6
．． 11-hexahydro-3,5,12-)dihydroxy-6,11-dioquine-3-(phenylcarbamoyloxy)methylnaphthacene, (IS)-cis-1-[(3
-amino-4-0-benzyl-2,3,6-drideoxy-α-L-lyxohexopyranosyl)oxy)-1,
2゜3.4,6.11-hexahydro-3,5,12-
Trihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene, 3.3'-[tetramethylenebis(carbamoyloxymethylene)bis-(IS)-cis-[(3-amino-2
,3,4,6-titradeoxy-α-L-threohexopyranosyl)oxy)-1゜2.3,4,6.11-hexahydro-3,5゜12-trihydroxy-6,11
-dioxonaphthacene, (IS)-cis-x-((a-amino-2,3°6-)
IJ deoxy-α-L-acypinohexopyranosyl)oxy]-a-(4-chlorophenylcarbamoyloxy)methyl-1,2,3,4,6゜11-hexahydro-
3,5,12-trihydroxy-6,11-dioquinaphthacene, (IS)-cis-1-(:(3-amino-2
,3゜6-drideoxy-α-L-arabinohequinpyranosyl)oxy: ]-a-(carpamoyloxy)methyl-1,2,3,4,6,11-hexahydro-3,
5,12-)rihydroxy-6.11-dioquinaphthacene, (IS)-cis-x-1:(a-amino-2,3°6-
Dorideoxy-α-L-arabinohexopyranosyl)oxy)-1,2,3,4,6,11-hexahydro-3
, 5, 12-) rihydroxy-6,11-dioxo-
3-[! (5)-(Phenylcarbamoyloxy)ethylfunaphthacene, (IS)-cis-1-1:(a-amino-2,16-drideoxy-4-0-methyl-α-
L-lyxohexopyranosyl)oxy)-1,2,3゜4 + 6 + 11-hexahydro-3,5,12-
) dihydroxy-6,11-dioxo-3-[1(R)
-(phenylcarbamoyloxy)ethylfunaphthacene, and pharmaceutically acceptable acid addition salts thereof. 13. A compound according to any one of claims 1 to 12 as a pharmaceutically active substance. 14. Claims 1 to 12 as an antitumor agent
A compound according to any of the paragraphs. 15. For producing the compound of formula I and the pharmaceutically acceptable acid addition salt thereof according to claim 1, (α) R is a hydrogen atom, lower alkyl, aryl or aryl- (lower alkyl) group, a 5- or 6-membered heteroaromatic group in which the hetero atom is nitrogen, oxygen or sulfur, or a group of formula (E) or (b) according to claim 1 To produce a compound of formula ■,
In the general formula, B (L is a hydrogen atom, trichloroacetyl, lower alkyl, aryl or aryl-(lower alkyl)
group, a 5- or 6-membered heteroaromatic group in which the heteroatom is oxygen or sulfur, a group of formula (α) according to claim 1 or a group of formula Claim 1
has the meaning given in Section 3, provided that any carboxy, hydroxy or amino group present in the aryol substituent is in protected form and any carboxy group present in group (α) is in protected form. In the general formula, R8 represents an amino protecting group, R'1 and R'2
each represents a hydrogen atom or R'! and RXt
one represents a hydrogen atom, and the other represents lower alkoxy,
benzyloxy, which still represents a protected hydroxy group, and cleaves one or more protecting groups present in the reaction product; A compound of the general formula % having the meaning given in paragraph 1, and Ra, Rtt and Rtt having the above meanings, wherein Rb is trichloroacetyl, lower alkyl, aryl or aryl-(lower alkyl) group, a 5- or 6-membered heteroaromatic group in which the heteroatom is nitrogen, oxygen or sulfur. The carboxy, hydroxy or amino group present in the group (α) shall be in a protected form, and the carboxy group present in the group (α) shall be in a protected form. has the meaning defined in claim 1, and cleaves one or more protecting groups present in the reaction product, or (C)R' has a lower alkoxy group. In order to prepare a compound of formula l, the corresponding compound of formula l, in which R' represents a hydroxy group, is suitably esterified, and (d) the compound of formula l is optionally rendered pharmaceutically acceptable. A process for producing a compound of formula I according to claim 1 and a pharmaceutically acceptable acid addition salt thereof, which comprises converting the compound of formula I into the acid addition salt obtained. 16. A pharmaceutical preparation containing a compound according to any of claims 1 to 12 and a compatible pharmaceutical carrier material. 17. Use of a compound according to any of claims 1 to 12 in the treatment of tumors. 18. The compound according to any one of claims 1 to 12, produced by the method according to claim 15 or a chemically equivalent method thereof. 19. In the general formula, R is a trichloroacetyl, lower alkyl, aryl or aryl-(lower alkyl) group, a 5- or 6-membered heteroaromatic group in which the hetero atom is nitrogen, oxygen or sulfur; represents a group of the formula (α) or a group of the formula described in Range 1, R8 represents an amino protecting group, each of R11 and R21 represents a hydrogen atom, or one of R'' and R2! is hydrogen; atom and the other represents lower alkoxy, benzyloxy or protected hydroxy, and n' and X have the meaning given in claim 1,
However, carboxy and hydroxy TFC present in the aryl substituent have all amino groups in a protected form,
And the carboxy group present in the group (α) is protected and in the mourning form. 20. General formula In the formula, R is a hydrogen atom, trichloroacetyl, lower alkyl, aryl or aryl-(lower alkyl) group,
5-membered or 6-membered heteroatom is 6 oxygen or sulfur
a heteroaromatic group of the formula (
a) represents a group or a group of the formula, n' and X have the meanings described in claim 1,
However, any carboxy, hydroxy or amino group present in the aryl substituent is in a protected form, and the carboxy group present in the group (α) is in a protected form. 21. A compound of the general formula, in which X has the meaning given in claim 1, and R", R" and R2 have the meaning given in claim 19.