JP2662607B2 - Bicyclo [8.3.0] trideca-9,13-diene-2,7-diyne derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to the following general formula (I) Wherein R ₁ and R ₂ are the same or different and each represent a hydrogen atom, a halogen atom, a hydroxyl group, an acyl group or a lower alkyl group, or R ₁ and R ₂ together represent an oxygen atom , R ₃ and R ₄ are the same or different and each represent a hydrogen atom or a lower alkyl group.] The present invention relates to a bicyclo [8.3.0] tridec-9,13-diene-2,7-diyne derivative.

[Conventional technology and its problems]

Neocarzinostatin, an antitumor antibiotic, is already used in gastric cancer,
It is widely used in clinical practice as a therapeutic agent for pancreatic cancer, acute leukemia and the like. This neocarzinostatin has a molecular weight
It is composed of 11000 protein parts and NCS-C with a molecular weight of 659. NCS-C is responsible for its antitumor activity and has the following structure [Tetrahedron Letters, 26, 331, 1985]. But this NC
It is known that SC is extremely unstable against heat and light (JP-B-60-30679).

[Means for Solving the Problems] Under such circumstances, the present inventors have conducted intensive studies to produce heat- and light-stable analogs and derivatives of NCS-C that are chemically synthesized. Bicyclo [7.3.0] dodeca-8,12-diene-2,6-diyne which is essential for the activity of C. Bicyclo [8.3.0] trideca-9,13-diene-similar to the ring
The 2,7-diyne derivative was successfully synthesized, and the obtained bicyclo [8.3.0] tridec-9,13-diene-2,7-diyne derivative was useful as an intermediate for producing NCS-C. NCS−
The present inventors have found that they have an antitumor activity similar to that of C, and completed the present invention.

That is, the present invention provides a bicyclo [8.3.0] tridec-9,13-diene-2,7-diyne derivative represented by the general formula (I).

The bicyclo [8.3.0] trideca-9,13-diene-2,7-diyne derivative of the present invention is a novel compound which has not been described in any literature, and may be produced, for example, according to the following methods 1) to 4). Can be.

1) According to the following formula, 3,3-dimethyl-4-pentynal (1) is produced from 2-methyl-3-butyn-2-ol.

2) From 2-cyclopentenone to 2-bromo-1- (2-propynyl) -2-cyclopentene- according to the following formula:
1-ol (2) is produced.

3) According to the following formula, 3,3-dimethyl-4-pentynal (1) and 2-bromo-1- (2-propynyl) -2-
Compound (7) is produced from cyclopenten-1-ol (2).

4) 4,4-dimethyl- from compound (7) according to the following formula:
Compound (8) (6-ketone) and compound (10) (6-acetyl) which are bicyclo [7.3.0] trideca-9,13-diene-2,3-diyne derivatives are produced.

The above synthesis method is an example, and if it is manufactured based on the same theory, it is possible to synthesize a derivative in which a halogen atom, a hydrogen atom, or the like is substituted at the 6-position and a hydrogen atom is substituted at the 4-position. Can be. Furthermore, like NCS-C, 11th place and 12th place
It is also possible to introduce an oxygen atom at the position.

〔Example〕

 Hereinafter, the present invention will be further described with reference to examples.

Example 1 Preparation of 2-chloro-2-methyl-3-butyne: 33.40 g of calcium chloride, 23.68 g of cuprous chloride and copper powder 0.4 g.
268 g and 250 ml of cold concentrated hydrochloric acid were added thereto under ice cooling, followed by stirring. The solution was cooled in an ice-salt bath and kept at 0-1 ° C.
58.0 ml of 2-methyl-3-butyn-2-ol is added dropwise within 30 minutes, and the mixture is further stirred for 1 hour. After stirring, the upper layer separated into two layers is separated by a separating funnel, washed twice with 60 ml of cold concentrated hydrochloric acid and three times with 60 ml of cold distilled water, and dried over anhydrous potassium carbonate. After the desiccant, calcium hydride was added under ice cooling, and the receiver was cooled (~ -50 ° C) under aspirator decompression (~ 10mmHg).
Further, the desired product is obtained by distillation and purification at room temperature.

Form: 37.98 g of colorless oil (yield 61.9%) Boiling point: 44 to 45 ° C./〜105 mmHg ¹ H-NMR (90 MHz, CDCl ₃ ) δ 1.87 (6H, s) 2.62 (1 H, s) IR (film) : Ν3300, 2975, 2926, 2061, 647 cm ^-1 Example 2 Production of ethyl 2-cyano-3,3-dimethyl-4-pentyate: Under an argon atmosphere, 520 ml of absolute ethanol was added to 7.24 g of lithium wire, and 40 ° C. Stir while cooling with ice.
When the lithium has completely dissolved, keep at 25 ° C. and add 119.4 ml of ethyl cyanoacetate. After stirring for a while, cuprous chloride and copper powder are added in an amount of about 200 mg each, and 58.6 ml of 2-chloro-2-methyl-3-butyne is slowly added dropwise while stirring at 30 ° C. or lower. After stirring at room temperature for 2 hours, 1N-hydrochloric acid (1043 ml) is added, and the mixture is extracted three times with ether (250 ml). 2 times with 250 ml of water, 125 m of saturated sodium bicarbonate water
l, Wash with 125 ml of saturated saline and dry with sodium sulfate. After removing the solvent, the residue is purified by silica gel column chromatography to obtain the desired product.

Form: yellow oil 70.64 g (75.5% yield) ¹ H-NMR (90 MHz, CDCl ₃ ) δ 1.33 (3 H, t, J = 7.2 Hz) 1.50 (6 H, s) 2.33 (1 H, s) 3.53 ( 1H, s) 4.29 (2H, q, J = 7.2Hz) IR (film): ν3285,2990,2110,1740,1250,1195,1034,6
57 cm ^-1 Example 3 Production of 3,3-dimethyl-4-pentynenitrile: Under an argon atmosphere, 51.61 g of potassium hydroxide and 281.2 ml of ethylene glycol were stirred while heating to 120 ° C.
After dissolution, 70.6 g of ethyl 2-cyano-3,3-dimethyl-4-pentynate is added, the mixture is kept at 120 ° C., stirred for 1.5 hours, and cooled to room temperature. 350 ml of cold water was added to this solution, and 200 ml of ether was added.
Extract three times. 3 times with 100 ml of water, 2 times with 100 ml of saturated saline
Wash twice and dry over magnesium sulfate. After distilling off ether at normal pressure, the desired product is obtained by distillation and purification under reduced pressure of an aspirator.

Form: colorless oil 25.42 g (60.2% yield) Boiling point: 83-84 ° C / 33 mmHg ¹ H-NMR (90 MHz, CDCl ₃ ) δ1.41 (6H, s) 2.25 (1H, s) 2.52 (2H, s Example 4 Production of 3,3-dimethyl-4-pentynal (1): Under an argon atmosphere, 25.4 g of 3,3-dimethyl-pentynenitrile and anhydrous dichloromethane 2 were stirred at -78 ° C, and DIBAH was added thereto. 261 ml of a 1 M hexane solution is slowly added dropwise. The mixture was left in a cooling medium with stirring to return to room temperature, 410 ml of a saturated aqueous ammonium chloride solution was added, and the mixture was stirred for 30 minutes.
Add 70 ml. The mixture was extracted three times with 200 ml of dichloromethane, washed with 300 ml of saturated saline, and dried over magnesium sulfate. Remove the solvent at low temperature and normal pressure. The desired product (1) is obtained by distillation and purification under reduced pressure of an aspirator.

Shape: colorless oily substance 20.14 g (yield 77.1%) Boiling point: 76-79 ° C./9090 mmHg ¹ H-NMR (90 MHz, CDCl ₃ ) δ1.34 (6H, s) 2.24 (1H, s) 2.43 (2H, d, J = 2.8Hz) 9.8
9 (1H, t, J = 2.8Hz) IR (film): ν3300,2933,2737,2100,1723,1367,645cm
^-1 Example 5 Preparation of 2-bromo-2-cyclopenten-1-one: 10 ml of 2-cyclopentenone and 120 ml of dichloromethane were stirred at 0 ° C., and a mixture of 6.15 ml of bromine and 120 ml of dichloromethane was added thereto. After dropwise addition for 30 minutes and stirring for 5 minutes, a mixture of 26.6 ml of triethylamine and 120 ml of dichloromethane was added dropwise at 0 ° C. or lower for 50 minutes, and the temperature was raised to room temperature for 1.5 minutes.
After stirring for an hour, an appropriate amount of hexane is added to precipitate the salt. After filtering the salt, the mixture is washed three times with 50 ml of 10% hydrochloric acid, twice with 50 ml of water and once with 100 ml of saturated saline, and dried with magnesium sulfate. The solvent is removed, and the residue is purified by silica gel column chromatography to obtain the desired product.

Shape: 17.26 g (yield 89.8%) of yellowish white solid Example 6 Production of 2-bromo-1- (2-propynyl) -2-cyclopenten-1-ol (2): Under an argon atmosphere, 5 ml of anhydrous diethyl ether was added. As a solvent, 226 mg of magnesium is reacted with 0.65 ml of propargyl bromide in the presence of 1 to 2 mg of mercury (II) chloride, and the mixture is heated under reflux for about 10 minutes. After allowing to cool to room temperature, 2-bromo-2
A solution of 933 mg of cyclopenten-1-one in 10 ml of ether is added. Since an oily substance precipitates, 10 ml of anhydrous tetrahydrofuran is added to make a homogeneous solution. After stirring for 10 minutes, 5 ml of water is added to stop the reaction. Further, 20 ml of water, 10 ml of a saturated aqueous ammonium chloride solution and saturated saline were added, and the mixture was added to ether.
Extract three times with 25 ml. The ether layer is washed with saturated saline (30 ml), dried over anhydrous sodium sulfate, concentrated, and the residue is purified by silica gel column chromatography to obtain the desired product (2).

Form: 904 mg of colorless oil (77% yield) ¹ H-NMR (200 MHz, CDCl ₃ ) δ 2.02 (t, 1 H, J = 2.5 Hz) 2.18 (s, 1 H, -OH) 2.22-2.52 (m, 4H) 2.55 (dd, 1H, J = 2.5,16.5Hz) 2.67
(Dd, 1H, J = 2.5,16.5Hz) 6.09 (t, 1H, J = 2.5Hz) IR (film): ν3400,3300,2930,2850,1620,1060,940,63
5 cm ^-1 Example 7 Production of compound (3): Under an argon atmosphere, 3.558 g of magnesium and anhydrous THF220
The mixture was stirred, and 11.19 ml of ethyl bromide was added thereto, followed by stirring at room temperature. When the magnesium solid disappears, 2-bromo-1- (2-propionyl) -2-cyclopentene-
A solution of 14.358 g of 1-ol (2) in 60 ml of anhydrous THF was added dropwise over 20 minutes, and the mixture was kept at 50 ° C. and stirred for 1 hour.
Lower to 25 ° C, 3,3-dimethyl-4-pentynal (1) 8.6
A mixture of 53 g and anhydrous THF 60 ml was added dropwise over 30 minutes, and 25
After stirring at 45 ° C. for 45 minutes, 120 ml of saturated aqueous ammonium chloride solution are added. The mixture was extracted three times with 100 ml of ether, washed with 200 ml of saturated saline, and dried over magnesium sulfate. The solvent is removed, and the residue is purified by silica gel column chromatography to obtain the desired product (3).

Shape: yellow-white solid 17.597 g of colorless columnar crystals after recrystallization
(Yield 79.2%) Melting point: 73 ° C. ¹ H-NMR (90 MHz, CDCl ₃ ) δ 1.29 (3H, s) 1.30 (3H, s) 1.83 (1H, d, J = 2.2 Hz) 1.9
0 (2H, d, J = 5.9Hz) 2.21 (1H, s) 2.27-2.52 (4H, m) 2.52 (1H, d, J = 1.8Hz) 2.62 (1H, dd, J = 1.8, 17.8Hz) 4 .
53-4.84 (1H, m) 6.06 ( 1H, t, J = 2.1Hz) Elemental analysis: C ₁₅ H ₁₉ O ₂ Br Calculated (%) C: 57.89, H : 6.15, Br: 25.67 Found (% C: 57.67, H: 6.14, Br: 25.93 Example 8 Preparation of Compound (4): 17.51 g of diol (3) and pyridine under an argon atmosphere
And stirred at room temperature until the diol is dissolved.
Chilled and add 10.39 ml of triethylsilyl chloride
, The mixture is returned to room temperature and stirred for 3 hours, and then 300 ml of saturated aqueous sodium hydrogen carbonate solution is added. The mixture is extracted three times with 75 ml of ether, washed with 100 ml of saturated saline and dried over magnesium sulfate. At the time of removing the solvent, azeotropic distillation with benzene is performed several times to remove pyridine to some extent, and then the residue is purified by silica gel column chromatography to obtain the desired product (4).

Form: 23.29 g of yellow oil (97.3% yield) ¹ H-NMR (90 MHz, CDCl ₃ ) δ0.67 (6H, q, J = 6.3 Hz) 0.98 (9H, t, J = 6.3 Hz) 1.28 (6H , s) 1.83 (2H, d, J = 5.9 Hz) 2.13 (1H, s) 2.24-2.47 (4H, m) 2.4-2.9 (2H, m) 4.69
(1H, t, J = 5.9Hz) 6.05 (1H, t, J = 2.2Hz) Example 9 Production of Compound (5): 8.01 g of alcohol (4) and anhydrous THF under an argon atmosphere.
190 ml was stirred at -78 ° C, and hexane solution of n-butyllithium (1.62 M) (24.7 mu) was slowly added dropwise thereto.
After stirring at −78 ° C. for 0 minute, tri-n-butyltin chloride
A mixture of 5.36 ml and 20 ml of anhydrous THF is added dropwise over 15 minutes, and the mixture is left with stirring for 17 hours, and 100 ml of saturated aqueous sodium hydrogen carbonate is added. The mixture was extracted twice with 20 ml of ether, washed with 30 ml of a saturated saline solution, re-extracted with ether, and dried over magnesium sulfate. The solvent is removed, and the residue is purified by silica gel column chromatography to obtain the desired product (5).

Shape: 12.67 g (yield 94.2%) of yellow oily substance ₁ H-NMR (90 MHz, CDCl ₃ ) δ 0.44-1.12 (42 H, m) 1.25 (6 H, s) 1.79 (2 H, d, J = 6.1 Hz) 2.08-2.20 (1H, m) 2.23-2.47 (4H, m) 2.51-2.75 (2H, m) 4.75 (1H, tt, J = 1.8,6.1Hz) 6.04 (1H, t, J = 1.6Hz) 10 Preparation of compound (6): Under an argon atmosphere, 12.67 g of alcohol (5) and anhydrous TH
F400ml and palladium tetrakistriphenylphosphine
The mixture with 857.3 mg is kept at 50 ° C. and stirred for 86 hours. After adding 500 ml of pentane, washing with 300 ml of 10% aqueous ammonia three times and washing with 300 ml of saturated saline, anhydrous magnesium sulfate is added and dried. After concentration, the residue is purified by silica gel column chromatography to obtain 4.404 g of alcohol (6) (1: 1 diastereomer mixture, yield 72.1%). Diastereomers can be separated by flash column chromatography, eluting with benzene.

Form: (6-a) pale yellow oily substance (6-b) pale yellow oily substance ₁ H-NMR (400 MHz, CDCl ₃ ) (6-a) δ0.65 (q, 6H, J = 8.0 Hz) 0.98 ( t, 9H, J = 8.0Hz) 1.26 (s, 3H) 1.28 (s, 3H) 1.67 (dd, 1H, J = 3.7,13.0Hz) 1.86 (ddd, 1H, J = 4.0,8.7,13.7Hz) 1.90 (Dd, 1H, J = 10.5, 13.0Hz) 2.09 (ddd, 1H, J = 5.6, 9.0, 13.7Hz) 2.32 (dddd, 1H, J = 2.8, 5.6, 8.7, 18.2Hz) 2.49 (dddd, 1H, J = 2.8,4.0,9.0,18.2Hz) 2.59 (dd, 1H, J = 3.0,16.6Hz) 2.65 (dd, 1H, J = 1.9,16.6Hz) 2.90 (s, 1H, -OH) 4.52 (dddd, 1H, J = 1.9,3.0,3.7,10.5Hz) 5.90 (t, 1H, J = 2.8Hz) (6-b) δ0.67 (q, 6H, J = 8.0Hz) 0.98 (t, 9H, J = 8.0Hz) 1.26 (s, 3H) 1.28 (s, 3H) 1.70 (dd, 1H, J = 4.0,13.2Hz) 1.85 (ddd, 1H, J = 3.8,8.6,13.6Hz) 1.98 (dd, 1H, J = 10.6, 13.2Hz) 2.10 (ddd, 1H, J = 5.8, 9.2, 13.6Hz) 2.32 (dddd, 1H, J = 2.7, 5.8, 8.6, 18.0Hz) 2.48 (dddd, 1H, J = 2.7, 3.8, 9.2, 18.0Hz) 2.59 (dd, 1H, J = 3.0, 16.8Hz) 2.64 (dd, 1H, J = 1.0, 16.8Hz) 4.53 (dddd, 1H, J = 1.0, 3.0, 4.0, 10.6Hz) 5.88 ( t, 1H, J 2.7 Hz) Example 11 Compound (7) Preparation of an argon atmosphere, the alcohol (6) 280.7Mg and THF1m
l, water (1 ml) and acetic acid (1 ml) were stirred at room temperature, and when the raw material disappeared by TLC, 10 ml of water was added. Extract three times with 10 ml of ethyl acetate, twice with 15 ml of saturated aqueous sodium bicarbonate, saturated saline
Wash with 15 ml and dry over magnesium sulfate. After concentration, the residue is purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain the desired diol (7).

Form: 161.9 mg of white plate crystals (86.3% yield) Melting point: 181-182 ° C ₁ H-NMR (400 MHz, CDCl ₃ ) δ 1.28 (3H, s) 1.30 (3H, s) 1.80 (1H, dd, J = 4.6,12.8Hz) 1.83 (1H, dd, J = 10.5,12.8Hz) 1.89 (1H, ddd, J = 4.0,8.5,13.8Hz) 2.11 (1H, ddd, J = 5.8,9.2,13.8Hz) 2.34 (1H, dddd, J = 2.8,5.8,8.4,18.0Hz) 2.49 (1H, dddd, J = 2.8,4.0,9.2,18.0Hz) 2.60 (1H, dd, J = 3.0,16.5Hz) 2.67 (1H , dd, J = 1.8,16.5Hz) 2.88 (1H, brs, -OH) 4.53 (1H, br ddd, J = 1.8,3.0,4.6,10.5Hz) 5.93 (1H, t, J = 2.8Hz) Implementation Example 12 Preparation of compound (8): Under an argon atmosphere, 0.473 ml of oxalyl chloride and 10.8 ml of anhydrous dichloromethane were stirred at -60 ° C, and a mixture of 0.643 ml of anhydrous dimethyl sulfoxide and 5.25 ml of anhydrous dichloromethane was added thereto. The mixture was added dropwise and stirred at -60 ° C for 10 minutes. Then, 0.25 g of diol (7) and 6.0 ml of anhydrous dichloromethane were added.
ml of dimethyl sulfoxide and 0.6 ml of anhydrous dimethylsulfoxide were slowly added dropwise.After stirring at -60 ° C for 30 minutes, 2.53 ml of anhydrous triethylamine was slowly added dropwise and added at -60 ° C for 30 minutes and at room temperature for 30 minutes. Stir and add 20 ml of water. Dichloromethane 15
Extract three times with ml and dry over magnesium sulfate. The solvent is removed, and the residue is purified by silica gel column chromatography to obtain the desired ketone (8).

Form: 0.165 g of white solid (72.3% yield) Melting point: Decomposed at 60 ° C. ¹ H-NMR (600 MHz, CDCl ₃ ): δ 1.30 (s, 6H, H ¹⁴ and H ¹⁵ ) 2.60 (ddt, 2H, J = 1.0,3.2,4.
^{9Hz, H 12) 2.62 (s} , 2H, H 5) 2.76 (br dt, 2H, J = 2.1,4.9H
^{z, H 11) 5.53 (dtt} , 1H, J = 1.4,1.0,2.1Hz, H 9) 6.58 (br
dt, 1H, J = 1.4,3.2Hz, H 13) 13 C-NMR (150MHz, CDCl 3): δ28.55 (CH 3, C 14, C 15) 30.90 (C, C 4) 31.02 (CH 2,
_{^{C 12) 31.40 (CH 2,}} C 11) 57.69 (CH 2, C 5) 77.61 (C, C 2) 9
4.70 (C, C ⁸ ) 96.25 (CH, C ⁹ ) 97.74 (C, C ⁷ ) 102.12 (C, C
^{3) 127.49 (C, C 1} ) 148.35 (CH, C 13) 165.91 (C, C 10) 18
^{5.89 (C, C 6) HRMS} (EI, 70eV), m / z, as C ₁₅ H ₁₄ O: Calculated 210.1045 (M ⁺⁾ Found ^{210.1042 (M +) IR (KBr} ): ν2974,2917,2869, 1637,1576,1361,1266,1249,1188,104
7,1001,956,928,804cm ^-1 Example 13 Production of Compound (9): 506.3 mg of diol (7) and pyridine under an argon atmosphere
0.311 ml of acetic anhydride is added to the mixture with 2.5 ml while stirring at 0 ° C., and the mixture is stirred at room temperature for 19 hours. 20 ml of a saturated aqueous solution of sodium hydrogencarbonate was added, and the mixture was extracted three times with 15 ml of ether. The organic phase was washed with 10 ml of saturated saline and dried over anhydrous magnesium sulfate. After concentration, the residue is purified by silica gel column chromatography to obtain the desired acetate (9).

Shape: colorless oil 594.7 mg (yield 99.4%) ¹ H-NMR (200 MHz, CDCl ₃ ) δ 1.30 (s, 3H) 1.33 (s, 3H) 1.74 (dd, 1H, J = 4.0, 13.0 Hz) 1.87 (ddd, 1H, J = 4.4, 8.5, 14.0 Hz) 1.93 (dd, 1H, J = 12.0, 13.0 Hz) 2.07 (s, 3H) 2.11 (ddd, 1H, J = 5.5, 8.8, 14.0 Hz) 2.32 (Dddd, 1H, J = 2.8,5.5,8.5,18.0Hz) 2.51 (dddd, 1H, J = 2.8,4.4,8.8,18.0Hz) 2.58 (dd, 1H, J = 3.0,16.5Hz) 2.70 (dd, 1H, J = 2.0,16.5Hz) 2.90 (br s, 1H, -OH) 5.55 (dddd, 1H, J = 2.0,3.0,4.0,12.0Hz) 5.93 (t, 1H, J = 2.8Hz) Preparation of compound (10): acetate (9) 172.
6.5 mg of dichloromethane solution of 7 mg, 155.5 mg of 4- (N, N-dimethylamino) pyridine and 1.77 ml of triethylamine
To this, 0.491 ml of methanesulfonyl chloride is added dropwise. 1
After stirring (0 ° C.) for 8 minutes, 10 ml of a saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted three times with 10 ml of ether. The organic layer was washed with 10 ml of a saturated saline solution and dried over anhydrous magnesium sulfate. The solution is concentrated under reduced pressure at 30 ° C. or less until the volume becomes about 1 ml, and purified by flash column chromatography (pentane: ether = 3: 1). Solvent removal is under reduced pressure (0.03mmHg) -5
By performing the reaction at 0 to -60 ° C, the desired acetate (10) is obtained.

Shape: colorless columnar crystals (recrystallized from ethyl acetate) 109.3 mg (68% yield) Melting point: 98-99.5 ° C (in a sealed tube) ¹ H-NMR (400 MHz, CDCl ₃ ): δ 1.31 (s, 3H, H) ^{15) 1.33 (s, 3H,} H 14) 1.78 (dd, 1H, J =
^{4.0,12.8Hz, H 5a) 2.01 (dd} , 1H, J = 10.6,12.8Hz, H 5b) 2.
^{09 (s, 3H, H 17} ) 2.49-2.54 (m, 2H, H 12) 2.63-2.68 (m, 2H, H 11) 5.34
(Ddtt, 1H, J = 1.2,1.5,1.0,2.1Hz , H 9) 5.69 (ddd, 1H, J
^{= 1.2,4.0,10.6Hz, H 6) 6.36 (} dtt, 1H, J = 1.5,0.6,3.2H
z, H ¹³ ) ¹³ C-NMR (150 MHz, CDCl ₃ ): δ 21.03 (CH ₃ , C ¹⁷ ) 25.71 (CH ₃ , C ¹⁴ ) 30.17 (C, C ⁴ ) 30.65 (CH ₂ , C ¹¹ ) 30.69 (CH _2, C ¹²⁾ 30.73
^{_{(CH 3, C 15) 45.02}} (CH 2, C 5) 63.22 (CH, C 6) 77.70 (C, C
^{2) 86.17 (C, C 8} ) 91.11 (C, C 7) 97.64 (CH, C 9) 101.66 (C, C 3) 127.44 (C, C 1) 144.61 (CH, C 13) 158.21
^{(C, C 10) 169.72 (} C, C 16) HRMS (EI, 70eV), m / z, calcd 254.1307 as _{C 17 H 18 O 2 (M} +) Found ^{254.1307 (M +) UVλmax (99.5} % ethanol ): 287 (logε4.23) 242 (3.63) 235 (sh, 3.55) IR (KBr): ν3030, 2980, 2915, 2870, 2840, 2250, 1728, 1603, 1448, 142
8,1377,1350,1280,1240,1207,1018,1013,960,820cm ^-1

Claims (1)

(57) [Claims] 1. The following general formula (I) Wherein R ₁ and R ₂ are the same or different and each represent a hydrogen atom, a halogen atom, a hydroxyl group, an acyl group or a lower alkyl group, or R ₁ and R ₂ together represent an oxygen atom , R ₃ and R ₄ are the same or different and each represent a hydrogen atom or a lower alkyl group.]. A bicyclo [8.3.0] tridec-9,13-diene-2,7-diyne derivative represented by the formula: