KR100846674B1 - The method of preparing optically active trans-alcohols and their esters by enzymatic method - Google Patents
The method of preparing optically active trans-alcohols and their esters by enzymatic method Download PDFInfo
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Abstract
본 발명은 라세믹 트랜스 알코올 화합물을 효소적 방법에 의해 광학활성 트랜스 알코올 화합물과 그의 에스테르 화합물로 제조하는 방법에 관한 것이다. 보다 상세하게 말하면, 용매상 또는 비용매상에서 라세믹 트랜스 알코올 화합물을 가수분해효소 또는 이를 포함하는 균주를 이용하여 입체 선택적으로 에스테르 반응하여 광학활성 트랜스 알코올 화합물과 그의 에스테르 화합물을 제조하는 것이다.The present invention relates to a process for preparing racemic trans alcohol compounds into optically active trans alcohol compounds and ester compounds thereof by enzymatic methods. To be more specific, it is to stereoselectively esterify a racemic trans alcohol compound using a hydrolase or a strain comprising the same to prepare an optically active trans alcohol compound and an ester compound thereof in a solvent phase or a nonsolvent phase.
리파제, 에스테르 반응, 트랜스 사이클로헥사놀 유도체, 트랜스 사이클로펜타놀 유도체 Lipase, ester reaction, trans cyclohexanol derivative, trans cyclopentanol derivative
Description
본 발명은 광학활성 트랜스 알코올 화합물 및 그의 에스테르 화합물 제조방법에 관한 것으로, 보다 구체적으로는 트랜스 알코올 화합물을 유기용매상 또는 비유기용매상에서 가수분해효소, 또는 이를 포함하는 균주를 이용하여 선택적으로 에스테르 반응하여 광학활성의 트랜스 알코올과 그의 에스테르로 제조하는 방법에 관한 것이다.The present invention relates to an optically active trans alcohol compound and a method for preparing an ester compound thereof, and more particularly, an ester reaction of a trans alcohol compound in an organic solvent or an inorganic solvent using a hydrolase, or a strain comprising the same. The present invention relates to a method of preparing an optically active trans alcohol and an ester thereof.
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Ajay 등(Tetrahedron:Asymmetry, vol. 5, 879-888, 1993)은 사이클로헥센(cyclohexene)에서 라세믹 트랜스 1-아세톡시 2-브로모 사이클로헥산(trans-1- acetoxy 2- bromocyclohexane)을 합성한 뒤 리파제를 이용하여 가수분해반응으로 광학활성의 트랜스 2- 브로모사이클로헥사놀(trans-2-bromocyclohexanol) 및 그의 에스테르를 제조하였다.Ajay the like (Tetrahedron:. Asymmetry, vol 5 , 879-888, 1993) is a racemic trans-1-acetoxy-2-bromo-cyclohexane (trans -1- acetoxy 2-bromocyclohexane) the synthesized in cyclohexene (cyclohexene) Later, lipase was used to prepare optically active trans- 2-bromocyclohexanol and its esters by hydrolysis.
Takada 등(Bulletin of the Chemical Society of Japan, vol. 67, 1196-1197, 1994)은 Pseudomonas cepacia lipase를 이용한 가수분해 반응으로 광학활성의 (1R,2R)-2-trans-t-butoxycarbonylaminocyclohexanol과 (1S,2S)-2-trans-t-butoxycarbonylaminocyclohexanol을 분리하였으나 효소의 사용량이 많고 반응시간이 길었다.Takada et al. (Bulletin of the Chemical Society of Japan, vol. 67, 1196-1197, 1994) described Pseudomonas Hydrolysis reaction with cepacia lipase separated optically active (1R, 2R) -2- trans -t-butoxycarbonylaminocyclohexanol and (1S, 2S) -2- trans -t-butoxycarbonylaminocyclohexanol, but the amount of enzyme was used and the reaction time was long. .
Faber(Tetrahedron Letters, vol. 29, 1903-1904, 1988) 등은 사이클로헥센 옥시드(cyclohexene oxide)에서 라세믹 트랜스-2-아지도사이클로헥사노에이트(trans-2-azidocyclohexanoate)를 합성한 다음 Candida cylindraces 리파제를 이용 하여 가수분해 반응을 통해 광학활성을 갖는 트랜스 2-아지도사이클로헥사놀(trans-2-azidocyclohexanol)을 제조하였다.Faber (Tetrahedron Letters, vol. 29, 1903-1904, 1988) et al. Synthesized racemic trans- 2-azidocyclohexanoate from cyclohexene oxide and then Candida Trans 2-azidocyclohexanol having optical activity was prepared through hydrolysis using cylindraces lipase.
Honig와 Seufer-Wasserthal은 (Synthesis, vol. 1137-1140, 1990)은 상온에서 리파제로 1~50시간 가수분해 반응하여 2번 위치에 치환기를 갖는 트랜스-2-치환된-사이클로헥실부타노에이트(trans-2-substituted-cyclohexylbutanoate)에서 광학활성의 트랜스-2-치환된-사이클로헥사놀 유도체를 생성하였다.Honig and Seufer-Wasserthal (Synthesis, vol. 1137-1140, 1990) were trans-2-substituted-cyclohexylbutanoate having a substituent at position 2 by hydrolysis reaction with lipase at room temperature for 1-50 hours. trans- 2-substituted-cyclohexylbutanoate) produced an optically active trans- 2-substituted-cyclohexanol derivative.
한편 Maestro 등(Tetrahedron: Asymmetry, vol 8, 3153-3159, 1997)은 리파제를 사용하여 에스테르 반응을 통해 광학활성을 갖는 트랜스 2-아미노사이클로헥사놀(trans-2-aminocyclohexanol)과 트랜스 2-아미노사이클로펜타놀(trans-2-amino cyclopentanol)을 생성하였다.On the other hand, Maestro et al. (Tetrahedron: Asymmetry, vol 8, 3153-3159, 1997) described trans- 2-aminocyclohexanol and trans 2-aminocyclo having optical activity through ester reaction using lipase. Pentanol ( trans- 2-amino cyclopentanol) was produced.
Luna 등(Tetrahedron: Asymmetry, vol. 9, 4483-4487, 1998)은 라세믹 시스-N-benzyloxycarbonyl-2-aminocylopentanol과 라세믹 시스-N-benzyloxycarbonyl-2-aminocylohexanol로부터 리파제를 이용해서 높은 광학활성을 갖는 시스-2-아미노사이클로펜타놀(cis-2-aminocyclopentanol)과 시스-2-아미노사이클로헥사놀(cis-2-aminocyclhexanol)을 생성하였다.Luna et al. (Tetrahedron: Asymmetry, vol. 9, 4483-4487, 1998) reported high optical activity using lipases from racemic cis-N-benzyloxycarbonyl-2-aminocylopentanol and racemic cis-N-benzyloxycarbonyl-2-aminocylohexanol. the cis-2-amino-cyclo-pentanol (cis -2-aminocyclopentanol) and cis-2-amino-cyclo-hexanol (cis -2-aminocyclhexanol) was generated with.
상기에서 언급한 바와 같이 리파제를 이용하여 가수분해 반응하여 광학활성의 2-치환된 사이클로헥사놀이나 2-치환된 사이클로펜타놀을 제조하는 연구나 2-아미노사이클로헥사놀이나 2-아미노사이클로펜타놀 유도체에서 에스테르 반응을 통해 광학순도를 높이는 연구는 보고된 바 있다. 그러나 2번 위치에 치환기가 첨가된 트랜스 사이클로헥사놀이나 트랜스 사이클로펜타놀을 에스테르 반응하여 광학활성 의 알코올과 그의 에스테르를 제조하는 방법은 보고된 바 없다. As mentioned above, studies have been made to produce an optically active 2-substituted cyclohexanol or 2-substituted cyclopentanol by hydrolysis using lipase, 2-aminocyclohexanol or 2-aminocyclopentanol. A study to increase the optical purity through the ester reaction in the derivative has been reported. However, no method of preparing an optically active alcohol and its ester by ester-reacting transcyclohexanol or trans cyclopentanol having a substituent added at the 2nd position has not been reported.
이에, 본 발명자들은 일반식 (1)로 표시되는 트랜스 알코올 화합물을 유기용매상 또는 비유기용매상에서 가수분해효소, 또는 이를 포함하는 균주를 이용하여 선택적으로 에스테르 반응하여 광학활성의 트랜스 알코올과 그의 에스테르로 제조하는 방법을 고안하였다.Accordingly, the present inventors selectively esterify the trans alcohol compound represented by the general formula (1) using a hydrolase, or a strain comprising the same, in an organic solvent or in an organic solvent, and thus an optically active trans alcohol and ester thereof. A method of manufacturing was devised.
본 발명에 의한 방법은 기존의 방법에 비해 반응이 간단하며 높은 광학 순도의 알코올과 그의 에스테르를 얻을 수 있다는 장점이 있다.The method according to the present invention has the advantage that the reaction is simpler than the conventional method and high optical purity of alcohol and its esters can be obtained.
따라서, 본 발명의 목적은 상기 [반응식 1]에서 일반식 (1)로 표시되는 라세믹 트랜스 화합물을 에스테르 반응하여 높은 수율과 광학 순도를 가지는 일반식 (2)로 표시되는 광학활성 트랜스 알코올과 일반식 (3)으로 표시되는 그의 에스테르를 제조하는 방법을 제공하는 데 있다.Therefore, an object of the present invention is a general reaction with the optically active trans alcohol represented by the general formula (2) having a high yield and optical purity by ester-reacting the racemic trans compound represented by the general formula (1) in the above [Scheme 1] It is providing the method of manufacturing the ester thereof represented by Formula (3).
또한 아실공여체로 무수숙신산을 사용하여 반응한 뒤, Na2CO3나 NaHCO3 등이 용해된 염기성 수용액을 가하여 추출하면 광학활성을 갖는 트랜스 알코올은 용매층으로 그의 에스테르는 수용액층으로 이동하게 되므로 생성물의 회수가 용이할 뿐만 아니라, 수용액층을 NaOH 등에 의해 가수분해하여 고수율과 높은 광학활성을 갖는 (1R,2R) 및 (1S,2S)- 트랜스 알코올 생성물을 한꺼번에 얻을 수 있다. In addition, the reaction is carried out using succinic anhydride as an acyl donor, followed by extraction by adding a basic aqueous solution of Na 2 CO 3 or NaHCO 3 dissolved, so that the transalcohol having optical activity is transferred to the solvent layer and its ester is transferred to the aqueous solution layer. Not only is easy to recover, but the aqueous layer can be hydrolyzed with NaOH or the like to obtain (1R, 2R) and (1S, 2S) -trans alcohol products having high yield and high optical activity at once.
상기 목적을 달성하기 위한 본 발명의 제조방법은 유기용매상 또는 비용매상에서 일반식 (1)로 표시되는 라세믹 트랜스 알코올 화합물을 가수분해효소 또는 이를 포함하는 균주를 첨가하여, 입체선택적으로 에스테르반응시키는 것으로 이루어 진다.The production method of the present invention for achieving the above object is a stereotransesterification of the racemic trans alcohol compound represented by the formula (1) in an organic solvent or a nonsolvent by adding a hydrolase or a strain comprising the same, and stereosterically esterifying It is made to make.
본 발명은 하기 [반응식 1]에서 일반식 (1)로 표시되는 라세믹 트랜스 알코올 화합물을 효소적 방법에 의해 각각 일반식 (2)와 (3)으로 표시되는 광학활성의 트랜스 알코올과 그의 에스테르로 제조하는 방법에 관한 것이다. 좀 더 상세하게 말하자면, 용매상 또는 비용매상에서 일반식 (1)로 표시되는 화합물을 가수분해효소 또는 이를 포함하는 균주를 이용하여 입체 선택적으로 에스테르 반응하여 일반식 (2)와 (3)으로 표시되는 광학활성 트랜스 알코올과 그의 에스테르로 제조하는 방법에 관한 것이다.
상기 식에서, n은 1 내지 4이고, X는 N3, CN, F, Cl, Br, I이며, R은 치환되거나 또는 치환되지 않은 탄소수 1 내지 8의 알킬기 또는 알케닐기, 벤질기, 탄소수 3 내지 6의 싸이클로알킬기, 치환되거나 치환되지 않은 아릴알킬기, 및 치환되거나 치환되지 않은 헤테로 아릴알킬기로 이루어진 군으로부터 선택되어 진다. 이때, 아실공여체(Acyldonor)는 비닐에스테르 화합물 또는 무수산 화합물로부터 선택된다.
또한, 본 발명은 하기 [반응식 1]에서 일반식(1)로 표시되는 라세믹 알코올 화합물을 아실공여체인 무수숙신산 용매에 첨가한 후, 가수분해효소 또는 이를 포함하는 균주를 촉매로 입체선택적으로 에스테르반응시켜 일반식(2)로 표시되는 광학활성 트랜스 알코올 화합물과 일반식(3)으로 표시되는 광학활성 에스테르 화합물을 제조한다.
[반응식 1]
상기 식에서, n은 1 내지 4이고, X는 N3, CN, F, Cl, Br, I이며, R은 치환되거나 또는 치환되지 않는 탄소수 1 내지 8의 알킬기 또는 알케닐기, 벤질기, 탄소수 3 내지 6의 싸이클로알킬기, 치환되거나 치환되지 않은 아릴알킬기, 및 치환되거나 치환되지 않은 헤테로 아릴알킬기로 이루어진 군으로부터 선택된다.
이때, 아실공여체(Acyldonor)로는 무수숙신산을 사용하며, 최종적으로 생성된 에스테르 화합물에서의 R은 CH2CH2COOH)이다.
본 발명을 좀 더 상세히 설명하면 다음과 같다.The present invention relates to a racemic transalcohol compound represented by the general formula (1) in the following Scheme 1 as an optically active transalcohol and its ester represented by the general formulas (2) and (3) by enzymatic methods, respectively. It relates to a manufacturing method. More specifically, the compound represented by the general formula (1) in the solvent or nonsolvent phase is subjected to stereoselective esterification using a hydrolase or a strain comprising the same, and represented by the general formulas (2) and (3). To an optically active trans alcohol and an ester thereof.
Wherein n is 1 to 4, X is N 3 , CN, F, Cl, Br, I, and R is a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms or alkenyl group, benzyl group, 3 to 3 carbon atoms 6 cycloalkyl group, substituted or unsubstituted arylalkyl group, and substituted or unsubstituted hetero arylalkyl group. At this time, the acyl donor is selected from a vinyl ester compound or an anhydride compound.
In addition, the present invention, after adding the racemic alcohol compound represented by the general formula (1) in the following [Scheme 1] to the succinic anhydride solvent, which is an acyl donor, the hydrolytic enzyme or a strain containing the same is stereoselectively esterified with a catalyst. The reaction is carried out to produce an optically active trans alcohol compound represented by the general formula (2) and an optically active ester compound represented by the general formula (3).
Scheme 1
Wherein n is 1 to 4, X is N 3 , CN, F, Cl, Br, I, R is substituted or unsubstituted alkyl group having 1 to 8 carbon atoms or alkenyl group, benzyl group, 3 to C carbon A cycloalkyl group of 6, a substituted or unsubstituted arylalkyl group, and a substituted or unsubstituted hetero arylalkyl group.
At this time, succinic anhydride is used as the acyldonor, and R in the finally produced ester compound is CH 2 CH 2 COOH).
The present invention is described in more detail as follows.
전술한 바와 같이, 본 발명에서는 유기용매 또는 유기용매 없이 아실 공여체만을 사용하여 반응물인 일반식 (1)로 표시되는 라세믹 트랜스 알코올에 가수분해효소 또는 이를 포함하는 균주를 첨가한 다음, 상기 혼합물을 일정온도에서 에스테르 반응시켜 광학활성 트랜스 알코올과 그의 에스테르로 제조한다.As described above, in the present invention, a hydrolase or a strain containing the same is added to the racemic trans alcohol represented by the general formula (1) using only an acyl donor without an organic solvent or an organic solvent, and then the mixture is The reaction is carried out at a constant temperature to prepare an optically active trans alcohol and an ester thereof.
본 발명에 사용되는 가수분해효소는 상업적으로 판매되는 것을 사용하거나 필요에 따라서는 제조하여 사용할 수 있다. 상업적으로 판매되는 리파제로는, 아마노 사의 PS, PS-D, AH와 노보자임스(Novozymes) 사의 CAL B 등의 리파제 효소를 들 수 있으며, 이에 한정되는 것은 아니다.The hydrolase used in the present invention can be used commercially available or can be prepared and used as needed. Commercially available lipases include, but are not limited to, lipase enzymes such as PS, PS-D, AH from Amano, and CAL B from Novozymes.
상기 에스테르 반응 후, 기존에 잘 알려진 방법에 의해 광학활성 트랜스 알코올 및 그의 에스테르로 각각 분리한다.After the ester reaction, each is separated into an optically active trans alcohol and its ester by a method well known in the art.
라세믹 트랜스 2-아지도사이클로헥사놀(trans-2-azidocyclohexanol)은 모세관(Capillary) 칼럼인 BP-1(SGE사, 30m×0.53mm)이 장착된 기체크로마토그래피(도남인스트루먼트사, 모델 DS 6200)를 이용하여 분석하였으며, 70℃에서 5분간 가열 후 220℃까지 분당 10℃씩 올려주었고, 220℃에서 10분을 유지하였다. 라세믹 트랜스 2-아지도사이클로헥사놀은 머무름시간(retention time)이 11.58분에서 검출되었으며, 트랜스 1-아세톡시 2-아지도사이클로헥산(trans-1-acetoxy 2-azido cyclohexane)은 머무름시간이 13.78분에서 검출되었으며, 트랜스 2-아지도 1-프로 피온옥시사이클로헥산(trans-2-azido 1-propionoxycyclohexane)은 머무름시간 13.59분에서 검출되었으며, 트랜스 2-아지도 1- 숙시닐옥시사이클로헥산 (trans-2-azido 1-succinyloxy cyclohexane)은 머무름시간 13.85분에서 검출되었다.Racemic trans 2-azidocyclohexanol is a gas chromatography (Donan Instruments, Model DS 6200) equipped with a capillary column, BP-1 (SGE, 30m × 0.53mm). 10 minutes per minute up to 220 ℃ after heating for 5 minutes at 70 ℃, was maintained at 220 ℃ 10 minutes. Racemic trans 2-azidocyclohexanol had a retention time of 11.58 minutes and trans- 1-acetoxy 2-azido cyclohexane had a retention time of Trans 2-azido 1-propionoxycyclohexane was detected at 13.78 minutes, and trans 2-azido 1-succinyloxycyclohexane was detected at 13.59 minutes. trans- 2-azido 1-succinyloxy cyclohexane) was detected at retention time of 13.85 minutes.
광학활성 (1R,2R)- 및 (1S,2S)-트랜스-2-아지도사이클로헥사놀은 키랄 컬럼(chiral column)인 AD-H(Daicel사)가 장착된 HPLC (Lab Alliance사, 모델 201)에서 헥산과 2-프로판올의 혼합물(95:5)을 0.7ml/min으로 흘려, 흡광도 220nm에서 분석하였다. (1R,2R)-트랜스-2-아지도사이클로헥사놀은 머무름 시간이 14.44분에서 검출되었으며 (1S,2S)-트랜스-2-아지도사이클로헥사놀은 머무름 시간이 16.51분에서 검출되었다. (1R,2R)-트랜스-1-아세톡시 2-아지도사이클로헥산은 머무름시간 7.34분에서 검출되었으며, (1S,2S)-트랜스-1-아세톡시 2-아지도사이클로헥산은 머무름시간 8.27분에서 검출되었다. (1R,2R)-트랜스-2-아지도 1-프로피온옥시사이클로헥산은 머무름시간 6.96분에서 검출되었으며, (1S,2S)-트랜스-2-아지도 1-프로피온옥시사이클로헥산은 머무름시간 6.10분에서 검출되었다. (1R,2R)-트랜스-2-아지도숙시닐옥시사이클로헥산은 머무름시간 20.42분에서 검출되었으며,(1S,2S)-트랜스-2-아지도숙시닐옥시사이클로헥산은 머무름시간 28.30분에서 검출되었다. Optically active (1R, 2R)-and (1S, 2S) -trans-2-azidocyclohexanol are HPLC (Lab Alliance, Model 201) equipped with a chiral column AD-H (Daicel) ), A mixture of hexane and 2-propanol (95: 5) was flowed at 0.7 ml / min, and the absorbance was analyzed at 220 nm. The (1R, 2R) -trans-2-azidocyclohexanol had a retention time of 14.44 minutes and the (1S, 2S) -trans-2-azidocyclohexanol had a retention time of 16.51 minutes. (1R, 2R) -trans-1-acetoxy 2-azidocyclohexane was detected at retention time 7.34 minutes, and (1S, 2S) -trans-1-acetoxy 2-azidocyclohexane was retention time 8.27 minutes Was detected in. (1R, 2R) -trans-2-azido 1-propionoxycyclohexane was detected at retention time of 6.96 minutes and (1S, 2S) -trans-2-azido 1-propionoxycyclohexane was stored at 6.10 minutes Was detected in. (1R, 2R) -trans-2-azidosuccinyloxycyclohexane was detected at retention time 20.42 minutes, and (1S, 2S) -trans-2-azidosuccinyloxycyclohexane was detected at retention time 28.30 minutes It became.
라세믹 트랜스 2-브로모사이클로헥사놀(trans-2-bromocyclohexanol)은 모세관(Capillary) 칼럼인 BP-1(SGE사, 30m×0.53mm)이 장착된 기체크로마토그래피(도남인스트루먼트사, 모델 DS 6200)를 이용하여 분석하였으며, 70℃에서 5분간 가열 후 220℃까지 분당 10℃씩 올려주었고, 220℃에서 10분을 유지하였다. 라세믹 트랜스 2-브로모사이클로헥사놀은 머무름시간 9.69분에서 검출되었고, 트랜스 1-아세톡 시 2-브로모사이클로헥산(trans-1-acetoxy 2-bromocyclohexane)은 머무름시간 13.97분에서 검출되었으며 트랜스 2-브로모 1-숙시닐옥시사이클로헥산(trans-2-bromo 1-succinyloxy cyclohexane)은 머무름시간 14.09분에서 검출되었다.Racemic trans 2-bromocyclohexanol is a gas chromatograph equipped with capillary column BP-1 (SGE, 30m × 0.53mm) (Donan Instruments, Model DS 6200). 10 minutes per minute up to 220 ℃ after heating for 5 minutes at 70 ℃, was maintained at 220 ℃ 10 minutes. Racemic trans 2-bromocyclohexanol was detected at retention time 9.69 minutes, trans 1-acetoxi 2-bromocyclohexane was detected at retention time 13.97 minutes and trans 2-bromo-1-oxy-succinyl cyclohexane (trans -2-bromo 1-succinyloxy cyclohexane) was detected at a retention time of 14.09 minutes.
광학활성 (1R,2R)- 및 (1S,2S)-트랜스-2-브로모사이클로헥사놀은 키랄 컬럼(chiral column)인 AD-H(Daicel사)가 장착된 HPLC (Lab Alliance사, 모델 201)에서 헥산과 2-프로판올의 혼합물(95:5)을 0.7ml/min으로 흘려, 흡광도 220nm에서 분석하였다. (1R,2R)-트랜스-2-브로모사이클로헥사놀은 머무름 시간이 14.38분에서 검출되었으며 (1S,2S)-트랜스-2-브로모사이클로헥사놀은 머무름 시간이 16.09분에서 검출되었다. (1R, 2R)-트랜스-1-아세톡시 2-브로모사이클로헥산은 머무름시간 6.48분에서 검출되었으며 (1S,2S)-트랜스-1-아세톡시 2-브로모사이클로헥산은 머무름시간 7.34분에서 검출되었다. (1R,2R)-트랜스-2-브로모 1-숙시닐옥시사이클로헥산은 머무름시간 7. 23분에서 검출되었으며 (1S,2S)-트랜스-2-브로모 1-숙시닐옥시사이클로헥산은 머무름시간 8.39분에서 검출되었다. Optically active (1R, 2R)-and (1S, 2S) -trans-2-bromocyclohexanol is HPLC (Lab Alliance, Model 201) equipped with chiral column AD-H (Daicel) ), A mixture of hexane and 2-propanol (95: 5) was flowed at 0.7 ml / min, and the absorbance was analyzed at 220 nm. The (1R, 2R) -trans-2-bromocyclohexanol had a retention time of 14.38 minutes and the (1S, 2S) -trans-2-bromocyclohexanol had a retention time of 16.09 minutes. (1R, 2R) -trans-1-acetoxy 2-bromocyclohexane was detected at retention time of 6.48 minutes and (1S, 2S) -trans-1-acetoxy 2-bromocyclohexane was detected at retention time of 7.34 minutes. Detected. (1R, 2R) -trans-2-bromo 1-succinyloxycyclohexane was detected at retention time 7.23 minutes and (1S, 2S) -trans-2-bromo 1-succinyloxycyclohexane was retained. It was detected at time 8.39 minutes.
라세믹 트랜스 2-시아노사이클로헥사놀(trans-2-cyanocyclohexanol)은 모세관(Capillary) 칼럼인 HP-FFAPP(J&W Scientific사, 30m×0.53mm)가 장착된 기체크로마토그래피(도남인스트루먼트사, 모델 DS 6200)를 이용하여 분석하였으며, 70℃에서 5분간 가열 후 220℃까지 분당 10℃씩 올려주었고, 220℃에서 10분을 유지하였다. 라세믹 트랜스 2-시아노사이클로헥사놀은 머무름시간(retention time) 20.08분에서 검출되었으며 트랜스 1-아세톡시 2-시아노사이클로헥산(trans-1-acetoxy 2-cyano cyclohexanol)은 머무름시간 17.81분에서 검출되었으며, 트랜스 2-시아노 1- 숙시닐옥시사이클로헥산(trans-2-cyano 1-succinyloxycyclohexane)은 머무름시간 22.82분에서 검출되었다.Racemic trans 2-cyanocyclohexanol is a gas chromatography (Donan Instruments, Model DS) equipped with HP-FFAPP (J & W Scientific, 30 m × 0.53 mm), a capillary column. 6200), and heated to 70 ℃ 10 minutes per minute after heating for 5 minutes at 70 ℃, it was maintained for 10 minutes at 220 ℃. Racemic trans 2-cyanocyclohexanol was detected at retention time 20.08 minutes and trans 1-acetoxy 2-cyano cyclohexanol at retention time 17.81 minutes Trans 2-cyano 1-succinyloxycyclohexane was detected at retention time of 22.82 minutes.
광학활성 트랜스 2-시아노사이클로헥사놀은 모세관(Capillary) 칼럼인 G-TA(astec사, 30m×0.32mm)가 장착된 기체크로마토그래피(도남인스트루먼트사, 모델 DS 6200)를 이용하여 분석하였으며, 70℃에서 5분간 가열 후 170℃까지 분당 10℃씩 올려주었고, 170℃에서 10분을 유지하였다. (1R,2R)-트랜스-2-시아노사이클로헥사놀은 머무름 시간이 19.52분에서 검출되었으며 (1S,2S)-트랜스-2-시아노사이클로헥사놀은 머무름 시간이 19.19분에서 검출되었다. (1R,2R)-트랜스-1-아세톡시 2-시아노사이클로헥산은 머무름시간 17.98분에서 검출되었으며 (1S,2S)-트랜스-1-아세톡시 2-시아노사이클로헥산은 머무름시간 16.88분에서 검출되었다. (1R,2R)-트랜스-2-시아노 1-숙시닐옥시사이클로헥산은 머무름시간 20.97분에서 검출되었으며 (1S,2S)-트랜스-2-시아노 1-숙시닐옥시사이클로헥산은 머무름시간 20.02분에서 검출되었다. Optically active trans 2-cyanocyclohexanol was analyzed using gas chromatography (Donam Instruments, Model DS 6200) equipped with a capillary column, G-TA (astec, 30 m × 0.32 mm). After heating at 70 ° C. for 5 minutes, the temperature was raised to 170 ° C. by 10 ° C. per minute and maintained at 170 ° C. for 10 minutes. The retention time of (1R, 2R) -trans-2-cyanocyclohexanol was detected at 19.52 minutes and the (1S, 2S) -trans-2-cyanocyclohexanol was detected at 19.19 minutes. (1R, 2R) -trans-1-acetoxy 2-cyanocyclohexane was detected at retention time 17.98 minutes and (1S, 2S) -trans-1-acetoxy 2-cyanocyclohexane was retained at 16.88 minutes Detected. (1R, 2R) -trans-2-cyano 1-succinyloxycyclohexane was detected at retention time 20.97 minutes and (1S, 2S) -trans-2-cyano 1-succinyloxycyclohexane was retention time 20.02 Detected in minutes.
라세믹 트랜스 2-클로로사이클로헥사놀(trans-2-chlorocyclohexanol)은 모세관(Capillary) 칼럼인 HP-FFAPP(J&W Scientific사, 30m×0.53mm)가 장착된 기체크로마토그래피(도남인스트루먼트사, 모델 DS 6200)를 이용하여 분석하였으며, 70℃에서 5분간 가열 후 220℃까지 분당 10℃씩 올려주었고, 220℃에서 10분을 유지하였다. 라세믹 트랜스 2-클로로사이클로헥사놀은 머무름시간(retention time)이 18.64분에서 검출되었으며 라세믹 트랜스 1-아세톡시 2-클로로사이클로헥산(trans-1-acetoxy 2-chlorocyclohexnaol)은 머무름시간(retention time)이 16.04분에서 검 출되었다.Racemic trans 2-chlorocyclohexanol is a gas chromatography (Donan Instruments, Model DS 6200) equipped with HP-FFAPP (J & W Scientific, 30m × 0.53mm), a capillary column. 10 minutes per minute up to 220 ℃ after heating for 5 minutes at 70 ℃, was maintained at 220 ℃ 10 minutes. Racemic trans 2-chlorocyclohexanol was detected at a retention time of 18.64 minutes, and racemic trans 1-acetoxy 2-chlorocyclohexnaol had a retention time. ) Was detected at 16.04 minutes.
광학활성 (1R,2R)- 및 (1S,2S)-트랜스-2-클로로사이클로헥사놀은 키랄 컬럼(chiral column)인 AD-H(Daicel사)가 장착된 HPLC (Lab Alliance사, 모델 201)를 이용하여 헥산과 2-프로판올의 혼합물(95:5)을 0.7ml/min으로 흘려, 흡광도 220nm에서 분석하였다. (1R,2R)-트랜스-2-클로로사이클로헥사놀은 머무름 시간 23.22분에서 검출되었으며 (1S,2S)-트랜스-2-클로로사이클로헥사놀은 머무름 시간 25.72분에서 검출되었다. (1R,2R)-트랜스-1-아세톡시 2-클로로사이클로헥산은 머무름시간 6.96분에서 검출되었으며, (1S,2S)-트랜스-1-아세톡시 2-클로로사이클로헥산은 머무름시간 7.71분에서 검출되었다. Optically active (1R, 2R)-and (1S, 2S) -trans-2-chlorocyclohexanol were HPLC (Lab Alliance, Model 201) equipped with chiral column AD-H (Daicel) The mixture (95: 5) of hexane and 2-propanol was flowed at 0.7 ml / min, and the absorbance was analyzed at 220 nm. (1R, 2R) -trans-2-chlorocyclohexanol was detected at retention time 23.22 minutes and (1S, 2S) -trans-2-chlorocyclohexanol was detected at retention time 25.72 minutes. (1R, 2R) -trans-1-acetoxy 2-chlorocyclohexane was detected at retention time 6.96 minutes, and (1S, 2S) -trans-1-acetoxy 2-chlorocyclohexane was detected at retention time 7.71 minutes It became.
라세믹 트랜스 2-아지도사이클로펜타놀(trans-2-azidocyclopentanol)은 모세관(Capillary) 칼럼인 BP-1(Astec사, 30m×0.32mm)가 장착된 기체크로마토그래피(도남인스트루먼트사, 모델 DS 6200)를 이용하여 분석하였으며, 70℃에서 5분간 가열 후 170℃까지 분당 10℃씩 올려주었고, 170℃에서 10분을 유지하였다. 라세믹 트랜스 2-아지도사이클로펜타놀은 머무름시간(retention time) 13.23분에서 검출되었다. 트랜스 1-아세톡시 2-아지도사이클로펜탄(trans-1-acetoxy 2-azidocyclo pentane)은 머무름시간 12.21분에서 검출되었으며 트랜스 2-아지도 1-숙시닐옥시사이클로펜탄(trans-2-azido 1-succinyloxycyclopentane)은 머무름시간 11.44분에서 검출되었다.Racemic trans 2-azidocyclopentanol is a gas chromatograph equipped with capillary column BP-1 (Astec, 30m × 0.32mm) (Donan Instruments, Model DS 6200). 10 minutes per minute up to 170 ℃ after heating for 5 minutes at 70 ℃, it was maintained for 10 minutes at 170 ℃. Racemic trans 2-azidocyclopentanol was detected at 13.23 minutes of retention time. Trans-1-acetoxy-2-O map cyclopentane (trans -1-acetoxy 2-azidocyclo pentane) was detected at a retention time of 12.21 minutes trans-2-azido-1-oxy-succinyl cyclopentane (trans -2-azido 1- Succinyloxycyclopentane) was detected at retention time 11.44 minutes.
광학활성 (1R,2R)- 및 (1S,2S)-트랜스-2-아지도사이클로펜타놀은 키랄 컬럼(chiral column)인 AS-H(Daicel사)가 장착된 HPLC (Lab Alliance사, 모델 201)를 이용하여 헥산과 2-프로판올의 혼합물(90:10)을 0.7ml/min으로 흘려, 흡광도 220nm에서 분석하였다. (1R,2R)-트랜스-2-아지도사이클로펜타놀은 머무름 시간이 9.12분에서 검출되었으며 (1S,2S)-트랜스-2-아지도사이클로펜타놀은 머무름 시간이 9.83분에서 검출되었다. (1R,2R)-트랜스-1-아세톡시 2-아지도사이클로헥산은 머무름시간 5.95분에서 검출되었으며 (1R,2R)-트랜스-1-아세톡시 2-아지도사이클로헥산은 머무름시간 7.70분에서 검출되었다. (1R,2R)-트랜스-2-아지도 1-숙시닐옥시사이클로펜탄은 머무름시간 10.65분에서 검출되었으며 (1S,2S)-트랜스-2-아지도 1-숙시닐옥시사이클로펜탄은 머무름시간 20.22분에서 검출되었다. Optically active (1R, 2R)-and (1S, 2S) -trans-2-azidocyclopentanol were HPLC (Lab Alliance, Model 201) equipped with AS-H (Daicel), a chiral column. The mixture of hexane and 2-propanol (90:10) was flowed at 0.7 ml / min, and the absorbance was analyzed at 220 nm. (1R, 2R) -trans-2-azidocyclopentanol was detected at retention time of 9.12 minutes and (1S, 2S) -trans-2-azidocyclopentanol was detected at retention time of 9.83 minutes. (1R, 2R) -trans-1-acetoxy 2-azidocyclohexane was detected at retention time 5.95 minutes and (1R, 2R) -trans-1-acetoxy 2-azidocyclohexane was detected at retention time 7.70 minutes. Detected. (1R, 2R) -trans-2-azido 1-succinyloxycyclopentane was detected at retention time 10.65 min and (1S, 2S) -trans-2-azido 1-succinyloxycyclopentane was retention time 20.22 Detected in minutes.
이하, 실시예를 통하여 본 발명을 좀 더 구체적으로 설명하지만, 하기 실시예에 본 발명의 범주가 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited to the following Examples.
실시예 1Example 1
라세믹 트랜스 2-아지도사이클로헥사놀은 사이클로헥센 옥시드(Cyclohexene oxide) 5g을 80% 에탄올 수용액에 녹인 후 NH4Cl 3.81g과 NaN3 4.3g을 서서히 적가시킨 뒤, 60℃에서 4시간 동안 반응하여 합성하였다. 합성한 라세믹 트랜스 2-아지도사이클로헥사놀은 아세트산 에틸(Ethyl acetate)로 추출하여 회수하였다.Racemic trans 2-azidocyclohexanol was dissolved in 5 g of cyclohexene oxide in an 80% aqueous ethanol solution and then slowly added dropwise to 3.81 g of NH 4 Cl and 4.3 g of NaN 3 for 4 hours at 60 ° C. Reaction was synthesized. The synthesized racemic trans 2-azidocyclohexanol was extracted with ethyl acetate and recovered.
트랜스 2-아지도사이클로헥사놀의 생성 여부는 FT-NMR(Bruker사 DRX 300)로 확인을 하였으며, 분석결과는 다음과 같다.The production of trans 2-azidocyclohexanol was confirmed by FT-NMR (Bruker DRX 300), and the analysis results are as follows.
1H-NMR δ= 3.3-3.5(br, 1H), 3.1-3.2(m, 1H), 2.2(t, 1H), 2.0-2.1(t, 3H), 1.7-1.8(br, 2H), 1.2-1.4(m, 4H)1 H-NMR δ = 3.3-3.5 (br, 1H), 3.1-3.2 (m, 1H), 2.2 (t, 1H), 2.0-2.1 (t, 3H), 1.7-1.8 (br, 2H), 1.2- 1.4 (m, 4H)
실시예 2Example 2
사이클로헥센 옥시드 5g에 30% 브롬산/아세트산 21ml를 적가시킨 뒤, 상온에서 반응하였다. 반응 종료 후, 아세트산 에틸로 추출하여 정제과정을 거쳐 라세믹 트랜스 1-아세톡시 2-브로모사이클로헥산을 제조하였다.To 5 g of cyclohexene oxide, 21 ml of 30% bromic acid / acetic acid was added dropwise, followed by reaction at room temperature. After completion of the reaction, the mixture was extracted with ethyl acetate and purified to prepare racemic trans 1-acetoxy 2-bromocyclohexane.
라세믹 트랜스 2-브로모사이클로헥사놀은 상기에서 제조한 트랜스 1-아세톡시 2-브로모사이클로헥산 3g에 HCl을 첨가하여 상온에서 가수분해 반응하여 합성하였다. 반응 종료 후, 중화과정을 거쳐 아세트산 에틸로 추출하여 회수하였다.The racemic trans 2-bromocyclohexanol was synthesized by hydrolysis at room temperature by adding HCl to 3 g of the trans 1-acetoxy 2-bromocyclohexane prepared above. After completion of the reaction, the mixture was neutralized and extracted with ethyl acetate.
트랜스 2-브로모사이클로헥사놀의 생성여부는 FT-NMR(Bruker사 DRX 300)로 확인을 하였으며, 분석결과는 다음과 같다.The production of trans 2-bromocyclohexanol was confirmed by FT-NMR (Bruker DRX 300), and the analysis results are as follows.
1H-NMR δ= 3.6-3.7(br, 1H), 3.3-3.4(m, 1H), 2.3(br, 1H), 2.0-1.9(t, 2H), 1.6-1.7(br, 2H), 1.2-1.3(m, 4H)1 H-NMR δ = 3.6-3.7 (br, 1H), 3.3-3.4 (m, 1H), 2.3 (br, 1H), 2.0-1.9 (t, 2H), 1.6-1.7 (br, 2H), 1.2- 1.3 (m, 4H)
실시예 3Example 3
라세믹 트랜스 2-시아노사이클로헥사놀은 증류수에 KCN 10g을 녹인 후 65% 황산을 첨가하여 pH 8을 맞춰주고, 사이클로헥센 옥시드 10.05g을 서서히 적가시켜 합성하였다. 반응 종료 후, 아세트산 에틸로 추출하여 회수하였다.Racemic trans 2-cyanocyclohexanol was synthesized by dissolving 10 g of KCN in distilled water, adding 65% sulfuric acid to adjust pH 8, and slowly adding dropwise 10.05 g of cyclohexene oxide. After completion of the reaction, the mixture was extracted with ethyl acetate and recovered.
트랜스 2-시아노사이클로헥사놀의 생성여부는 FT-NMR(Bruker사 DRX 300)로 확인을 하였으며, 분석결과는 다음과 같다.The production of trans 2-cyanocyclohexanol was confirmed by FT-NMR (Bruker DRX 300), and the analysis results are as follows.
1H-NMR δ= 3.73(m, 1H), 2.43(m, 2H), 2.10(m, 2H), 1.71(m, 2H), 1.61(m, 1H), 1.30(m, 3H)1H-NMR δ = 3.73 (m, 1H), 2.43 (m, 2H), 2.10 (m, 2H), 1.71 (m, 2H), 1.61 (m, 1H), 1.30 (m, 3H)
실시예 4Example 4
라세믹 트랜스 2-클로로사이클로헥사놀은 사이클로헥센 옥시드 10g을 증류수 에 녹인 뒤, 염산(HCl, 35%)을 20ml 적가시켜 합성하였다. 반응 종료 후, 중화과정을 거쳐 아세트산 에틸로 추출하여 회수하였다.Racemic trans 2-chlorocyclohexanol was synthesized by dissolving 10 g of cyclohexene oxide in distilled water and then adding 20 ml of hydrochloric acid (HCl, 35%) dropwise. After completion of the reaction, the mixture was neutralized and extracted with ethyl acetate.
트랜스 2-클로로사이클로헥사놀의 생성여부는 FT-NMR(Bruker사 DRX 300)로 확인을 하였으며, 분석결과는 다음과 같다.The production of trans 2-chlorocyclohexanol was confirmed by FT-NMR (Bruker DRX 300), the analysis results are as follows.
1H-NMR δ= 3.4-3.5(t 1H), 1.7-1.6(s, 2H), 3.3-3.2(q, 1H), 2.1-1.9(d, 2H), 1.7-1.6(s, 2H), 1.4-1.2(t, 4H)1H-NMR δ = 3.4-3.5 (t 1H), 1.7-1.6 (s, 2H), 3.3-3.2 (q, 1H), 2.1-1.9 (d, 2H), 1.7-1.6 (s, 2H), 1.4 -1.2 (t, 4H)
실시예 5Example 5
라세믹 트랜스 2-아지도사이클로펜타놀은 사이클로펜텐 옥시드(cyclopentene oxide) 2g을 80% 에탄올 수용액에 녹인 후 NH4Cl 1.55g과 NaN3 1.64g을 서서히 적가시킨 뒤, 70℃에서 7시간 동안 반응하여 합성하였다. 합성한 라세믹 트랜스 2-아지도사이클로펜타놀은 아세트산 에틸(Ethyl acetate)로 추출하여 회수하였다.Racemic trans 2-azidocyclopentanol was dissolved in 2 g of cyclopentene oxide in an aqueous 80% ethanol solution and then slowly added dropwise to 1.55 g of NH 4 Cl and 1.64 g of NaN 3 for 7 hours at 70 ° C. Reaction was synthesized. The synthesized racemic trans 2-azidocyclopentanol was recovered by extraction with ethyl acetate.
2-아지도사이클로펜타놀의 생성여부는 FT-NMR(Bruker사 DRX 300)로 확인을 하였으며, 분석결과는 다음과 같다.The production of 2-azidocyclopentanol was confirmed by FT-NMR (Bruker DRX 300), and the analysis results are as follows.
1H-NMR δ= 4.0-4.2(br q, 1H), 3.6-3.8(br q, 1H), 2.1-1.9(m, 2H) 1.5-1.8(m, 4H)1H-NMR δ = 4.0-4.2 (br q, 1H), 3.6-3.8 (br q, 1H), 2.1-1.9 (m, 2H) 1.5-1.8 (m, 4H)
실시예 6Example 6
라세믹 트랜스 2-아지도사이클로헥사놀 0.05g을 t-부틸메틸에테르(tert-butylmethylether) 4.9ml와 아세트산비닐(vinyl acetate) 50㎕가 들어있는 바이알(vial)에 녹인 다음 리파제 PS-D를 0.05g이 되도록 넣은 다음 30℃에서 반응을 수행하였다. 반응물질의 분석 결과는 하기 표 1에 나타내었다.0.05 g of racemic trans 2-azidocyclohexanol is dissolved in a vial containing 4.9 ml of tert-butylmethylether and 50 µl of vinyl acetate, followed by lipase PS-D of 0.05. g was added and the reaction was carried out at 30 ° C. The analysis results of the reactants are shown in Table 1 below.
실시예 7Example 7
리파제 PS-D 대신에 Novozym435(Novozymes사)를 실시예 6과 동일하게 실시하였으며, 반응물질의 분석 결과는 하기 표 1에 나타내었다.Instead of lipase PS-D Novozym435 (Novozymes) was carried out in the same manner as in Example 6, the analysis results of the reactants are shown in Table 1 below.
실시예 8 Example 8
리파제 PS-D 대신에 리파제 AH (Amano사)를 사용하여 실시예 6과 동일하게 실시하였으며, 반응물질의 분석 결과는 하기 표 1에 나타내었다. Instead of lipase PS-D, lipase AH (manufactured by Amano) was used in the same manner as in Example 6, and the analysis results of the reactants are shown in Table 1 below.
실시예 9Example 9
아세트산비닐 대신에 프로피온산비닐(vinyl propionate)을 실시예 6과 동일하게 실시하였으며, 반응물질의 분석결과는 하기 표 2에 나타내었다.Vinyl propionate (vinyl propionate) was carried out in the same manner as in Example 6 instead of vinyl acetate, and the analysis results of the reactants are shown in Table 2 below.
실시예 10Example 10
아세트산비닐 대신에 무수숙신산(succinic anhydride)을 실시예 6과 동일하게 실시하였으며, 반응물질의 분석결과는 하기 표 2에 나타내었다.Succinic anhydride was performed in the same manner as in Example 6 instead of vinyl acetate, and the analysis results of the reactants are shown in Table 2 below.
실시예 11Example 11
아세트산 비닐 대신에 무수부틸산(butyric anhydride)을 실시예 6과 동일하게 실시하였으며, 반응물질의 분석결과는 하기 표 2에 나타내었다.Butyric anhydride was carried out in the same manner as in Example 6 instead of vinyl acetate, and the analysis results of the reactants are shown in Table 2 below.
실시예 12Example 12
라세믹 트랜스 2-아지도사이클로헥사놀 대신에 라세믹 트랜스 2-시아노사이클로헥사놀을 실시예 6과 동일하게 실시하였으며, 반응물질의 분석 결과는 하기 표 3에 나타내었다.Instead of racemic trans 2-azidocyclohexanol, racemic trans 2-cyanocyclohexanol was carried out in the same manner as in Example 6, and the analysis results of the reactants are shown in Table 3 below.
실시예 13Example 13
라세믹 트랜스 2-아지도사이클로헥사놀 대신에 라세믹 트랜스 2-클로로사이클로헥사놀을 실시예 6과 동일하게 실시하였으며, 반응물질의 분석 결과는 하기 표 3에 나타내었다.Instead of racemic trans 2-azidocyclohexanol, racemic trans 2-chlorocyclohexanol was carried out in the same manner as in Example 6, and the analysis results of the reactants are shown in Table 3 below.
실시예 14Example 14
라세믹 트랜스 2-아지도사이클로헥사놀 대신에 라세믹 트랜스 2-브로모사이클로헥사놀을 실시예 6과 동일하게 실시하였으며, 반응물질의 분석 결과는 하기 표 3에 나타내었다.Instead of racemic trans 2-azidocyclohexanol, racemic trans 2-bromocyclohexanol was carried out in the same manner as in Example 6, and the analysis results of the reactants are shown in Table 3 below.
실시예 15Example 15
라세믹 트랜스 2-아지도사이클로헥사놀 대신에 라세믹 트랜스 2-아지도사이클로펜타놀을 실시예 6과 동일하게 실시하였으며, 반응물질의 분석 결과는 하기 표 3에 나타내었다.Instead of racemic trans 2-azidocyclohexanol, racemic trans 2-azidocyclopentanol was carried out in the same manner as in Example 6, and the analysis results of the reactants are shown in Table 3 below.
실시예 16Example 16
용매인 t-부틸메틸에테르 대신에 아실공여체인 아세트산 비닐만 4.95ml 첨가하고 실시예 6과 동일하게 실시하였으며, 반응물질의 분석 결과는 하기 표 4에 나타내었다.Instead of the solvent t-butyl methyl ether, only 4.95ml of acyl donor vinyl acetate was added thereto, and the same procedure as in Example 6 was carried out. The analysis results of the reactants are shown in Table 4 below.
실시예 17Example 17
반응물로 라세믹 트랜스 2-아지도사이클로헥사놀을, 아세트산비닐 대신에 무수숙신산을 아실공여체로 사용하여 실시예 6과 동일하게 실시하였으며, 반응 후 (1R,2R)-트랜스-2-아지도1-숙시닐옥시사이클로헥산은 일정량의 Na2CO3가 포함된 수용액을 가하여 추출한 뒤 NaOH에 의해 가수분해하여 (1R,2R)-트랜스-2-아지도사이클로헥사놀로 획득하였다. 반응 후 (1S,2S)- 및(1R,2R)-트랜스-아지도사이클로헥사놀의 분석결과는 하기 표 5에 나타내었다.As a reaction, racemic trans 2-azidocyclohexanol was carried out in the same manner as in Example 6 using acyl donor instead of vinyl acetate as acyl donor. -Succinyloxycyclohexane was extracted by adding an aqueous solution containing a certain amount of Na 2 CO 3 and then hydrolyzed with NaOH to obtain (1R, 2R) -trans-2-azidocyclohexanol. The analysis results of (1S, 2S)-and (1R, 2R) -trans-azidocyclohexanol after the reaction are shown in Table 5 below.
실시예 18Example 18
반응물로 라세믹 트랜스 2-브로모사이클로헥사놀을 사용하여 실시예 17와 동일하게 실시하였으며, 반응물질의 분석결과는 하기 표 5에 나타내었다.The reaction was carried out in the same manner as in Example 17 using racemic trans 2-bromocyclohexanol, the analysis results of the reactants are shown in Table 5 below.
실시예 19Example 19
반응물로 라세믹 트랜스 2-시아노사이클로헥사놀을 사용하여 실시예 17와 동일하게 실시하였으며, 반응물질의 분석결과는 하기 표 5에 나타내었다.The reaction was carried out in the same manner as in Example 17 using racemic trans 2-cyanocyclohexanol, the analysis results of the reactants are shown in Table 5 below.
실시예 20Example 20
반응물로 라세믹 트랜스 2-아지도사이클로펜타놀을 사용하여 실시예 17와 동일하게 실시하였으며, 반응물질의 분석결과는 하기 표 5에 나타내었다.The reaction was carried out in the same manner as in Example 17 using racemic trans 2-azidocyclopentanol, and the analysis results of the reactants are shown in Table 5 below.
상기 실시예 6~20을 통해 알 수 있는 것과 같이, 광학활성 트랜스 알코올 및 그 에스테르를 제조하는 방법에 있어서 본 발명에 따른 제조방법은 가수분해효소 또는 이를 포함하는 균주를 사용하는 에스테르 반응으로 높은 광학 순도를 갖는 사이클로알코올 유도체 및 그의 에스테르를 얻을 수 있을 뿐만 아니라, 반응 후 생성물의 회수가 쉬워 실제 공정에 적용하기 쉽다. 또한 반응에 사용하는 생촉매는 손쉽게 회수하여 재사용이 가능하므로 산업상 매우 유용하다.As can be seen through Examples 6 to 20, in the method for producing an optically active trans alcohol and ester thereof, the production method according to the present invention is a high optical reaction by using a hydrolase or a strain comprising the same In addition to obtaining cycloalcohol derivatives and esters thereof with purity, the recovery of the product after the reaction is easy and easy to apply to actual processes. In addition, the biocatalyst used in the reaction is very useful in industry because it can be easily recovered and reused.
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US5750382A (en) | 1995-08-04 | 1998-05-12 | Kaneka Corporation | Process for producing optically active 2-alkoxycyclohexanol derivatives |
KR0160500B1 (en) * | 1989-08-25 | 1999-01-15 | 노기 사다오 | Optically active cyclopentenols and process for preparing the same |
WO2002004384A2 (en) | 2000-07-07 | 2002-01-17 | Csir | Process for preparing (-)menthol and similar compounds |
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KR0160500B1 (en) * | 1989-08-25 | 1999-01-15 | 노기 사다오 | Optically active cyclopentenols and process for preparing the same |
US5750382A (en) | 1995-08-04 | 1998-05-12 | Kaneka Corporation | Process for producing optically active 2-alkoxycyclohexanol derivatives |
WO2002004384A2 (en) | 2000-07-07 | 2002-01-17 | Csir | Process for preparing (-)menthol and similar compounds |
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