Asymmetric Bioreduction of 3,5-Bis(trifluoromethyl) Acetophenone to Its Corresponding Alcohol by Candida tropicalis

›› 2011, Vol. 19 ›› Issue (6): 1028-1032.

Asymmetric Bioreduction of 3,5-Bis(trifluoromethyl) Acetophenone to Its Corresponding Alcohol by Candida tropicalis

王普¹, 苏会贞¹, 孙立明¹, 何军邀², 吕亚萍¹

1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China;
2. Zhejiang Pharmaceutical College, Ningbo 315100, China

收稿日期:2010-11-18 修回日期:2011-08-06 出版日期:2011-12-28 发布日期:2012-04-24
通讯作者: WANG Pu, E-mail: wangpu@zjut.edu.cn
基金资助:
Supported by the National Natural Science Foundation of China (21076193);Foundation of Zhejiang Key Developing Discipline of Pharmacy (20100609)

Asymmetric Bioreduction of 3,5-Bis(trifluoromethyl) Acetophenone to Its Corresponding Alcohol by Candida tropicalis

WANG Pu¹, SU Huizhen¹, SUN Liming¹, HE Junyao², LÜ Yaping¹

1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China;
2. Zhejiang Pharmaceutical College, Ningbo 315100, China

Received:2010-11-18 Revised:2011-08-06 Online:2011-12-28 Published:2012-04-24
Supported by:
Supported by the National Natural Science Foundation of China (21076193);Foundation of Zhejiang Key Developing Discipline of Pharmacy (20100609)

摘要/Abstract

摘要： (S)-3,5-bistrifluoromethylphenyl ethanol is a key chiral intermediate for the synthesis of NK-1 receptor antagonists. Enantioselective synthesis of (S)-3,5-bistrifluoromethylphenyl ethanol was successfully performed in high enantiomeric excess (e.e.) through asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone catalyzed by Candida tropicalis 104 cells. The influence of some key reaction parameters such as substrate concentration, co-substrate and its concentration, biomass and reaction time was examined, respectively. The results showed that these factors obviously influence the yield, but the optical purity of the prepared product remains intact. The optimum conditions for the preparation of (S)-3,5-bistrifluoromethylphenyl ethanol were found to be as follows: substrate concentration 50 mmol·L^-1; 50 g·L^-1 of maltose as co-substrate; wet cell concentration 300 g·L^-1; reaction for 30 h. Under above optimal conditions, the maximum yield for (S)-3,5-bistrifluoromethylphenyl ethanol reached 70.3% with 100% of product e.e.

关键词: Candida tropicalis, asymmetric reduction, enantioselectivity, 3,5-bis(trifluoromethyl) acetophenone, (S)-3,5-bistrifluoromethylphenyl ethanol

Abstract: (S)-3,5-bistrifluoromethylphenyl ethanol is a key chiral intermediate for the synthesis of NK-1 receptor antagonists. Enantioselective synthesis of (S)-3,5-bistrifluoromethylphenyl ethanol was successfully performed in high enantiomeric excess (e.e.) through asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone catalyzed by Candida tropicalis 104 cells. The influence of some key reaction parameters such as substrate concentration, co-substrate and its concentration, biomass and reaction time was examined, respectively. The results showed that these factors obviously influence the yield, but the optical purity of the prepared product remains intact. The optimum conditions for the preparation of (S)-3,5-bistrifluoromethylphenyl ethanol were found to be as follows: substrate concentration 50 mmol·L^-1; 50 g·L^-1 of maltose as co-substrate; wet cell concentration 300 g·L^-1; reaction for 30 h. Under above optimal conditions, the maximum yield for (S)-3,5-bistrifluoromethylphenyl ethanol reached 70.3% with 100% of product e.e.

Key words: Candida tropicalis, asymmetric reduction, enantioselectivity, 3,5-bis(trifluoromethyl) acetophenone, (S)-3,5-bistrifluoromethylphenyl ethanol

王普, 苏会贞, 孙立明, 何军邀, 吕亚萍. Asymmetric Bioreduction of 3,5-Bis(trifluoromethyl) Acetophenone to Its Corresponding Alcohol by Candida tropicalis[J]. , 2011, 19(6): 1028-1032.

WANG Pu, SU Huizhen, SUN Liming, HE Junyao, LÜ Yaping. Asymmetric Bioreduction of 3,5-Bis(trifluoromethyl) Acetophenone to Its Corresponding Alcohol by Candida tropicalis[J]. , 2011, 19(6): 1028-1032.

参考文献

1 Chartrain, M., Greasham, R., Moore, J., Reider, P., Robinson, D., Buckland, B., “Asymmetric bioreductions: application to the synthesis of pharmaceuticals”, J. Mol. Catal. B: Enzym., 11(4-6), 503-512(2001).
2 Patel, R.N., “Microbial/enzymatic synthesis of chiral intermediates for pharmaceuticals”, Enzyme Microb. Technol., 31(6), 804-826(2002).
3 Nakamuraetal, K., Yamanaka, R., Matsuda, T., Harada, T., “Recent developments in asymmetric reduction of ketones with biocatalysts”, Tetrahedron: Asymmetry, 14(18), 2659-2681(2003).
4 Hansen, K.B., Chilenski, J.R., Desmond, R., Devine, P.N., Grabowski, E.J.J., Heid, R., Kubryk, M., Mathrea, D.J., Varsolonab, R., “Scalable, efficient process for the synthesis of(R)-3,5bistrifluoromethylphenyl ethanol via catalytic asymmetric transfer hydrogenation and isolation as a DABCO inclusion complex”, Tetrahedron: Asymmetry, 14(22), 3581-3587(2003).
5 Li, Y.N., Shi, X.A., Zong, M.H., Meng, C., Dong, Y.Q., Guo, Y.H., “Asymmetric reduction of 2-octanone in water/organic solvent biphasic system with Baker’s yeast FD-12”, Enzyme Microb. Technol., 40(5), 1305-1311(2007).
6 Chang, X., Yang, Z.H., Zeng, R., Yang, G., Yan, J.B., “Production of chiral aromatic alcohol by asymmetric reduction with vegetable catalyst”, Chin. J. Chem. Eng., 18(6), 1029-1033(2010).
7 Ema, T., Yagasaki, H., Okita, N., Nishikawa, K., Korenaga, T., Sakai, T., “Asymmetric reduction of a variety of ketones with a recombinant carbonyl reductase: identification of the gene encoding a versatile biocatalyst”, Tetrahedron: Asymmetry, 16(6), 1075-1078(2005).
8 Zhu, D.M., Malik, H.T., Hua, L., “Asymmetric ketone reduction by a hyperthermophilic alcohol dehydrogenase. The substrate specificity, enantioselectivity and tolerance of organic solvents”, Tetrahedron: Asymmetry, 17(21), 3010-3014(2006).
9 Jung, J., Park, H.J., Uhm, K.N., Kim, D., Kim, H.K., “Asymmetric synthesis of(S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: Enantioselectivity and enzyme-substrate docking studies”, Biochimica et Biophysica Acta, 1804(9), 1841-1849(2010).
10 Li, N., Ni, Y., Sun, Z.H., “Purification and characterization of carbonyl reductase from Candida krusei SW2026 involved in enantioselective reduction of ethyl 2-oxo-4-phenylbutyrate”, J. Mol. Catal. B: Enzym., 66(1-2), 190-197(2010).
11 Kurbanoglu, E.B., Zilbeyaz, K., Ozdal, M., Taskin, M., Kurbanoglu, N.I., “Asymmetric reduction of substituted acetophenones using once immobilized Rhodotorula glutinis cells”, Bioresource Technol., 101, 3825-3829(2010).
12 Xiao, M.T., Ye, J., Zhang, Y.W., Huang, Y.Y., “Reaction characteristics of asymmetric synthesis of(2S, 5S)-2,5-hexanediol catalyzed with baker’s yeast number 6”, Chin. J. Chem. Eng., 17(3), 493-499(2009).
13 Homann, M.J., Vail, R.B., Previte, E., Tamarez, M., Morgan, B., Dodds, D.R., Zaks, A., “Rapid identification of enantioselective ketone reductions using targeted microbial libraries”, Tetrahedron, 60(3), 789-797(2004).
14 Mandal, D., Ahmad, A., Khan, M.I., Kumar, R., “Enantioselective bioreduction of acetophenone and its analogous by the fungus Trichothecium sp.”, J. Mol. Catal. B: Enzym., 27(2-3), 61-63(2004).
15 Yang, W., Xu, J.H., Xie, Y., Xu, Y., Zhao, G., Lin, G.Q., “Asymmetric reduction of ketones by employing Rhodotorula sp. AS 2.2241 and synthesis of the β-blocker(R)-nifenalol”, Tetrahedron: Asymmetry, 17(12), 1769-1774(2006).
16 Gelo-Pujic, M., Guyader, F.L., Schlama, T., “Microbial and homogenous asymmetric catalysis in the reduction of 1-[3,5-bis(trifluoromethyl)phenyl] ethanone”, Tetrahedron: Asymmetry, 17(13), 2000-2005(2006).
17 Pollard, D., Truppo, M., Pollard, J., Chen, C.Y., Moore, J., “Efficient synthesis of(S)-3,5-bistrifluoromethylphenyl ethanol by asymmetric enzymatic reduction”, Tetrahedron: Asymmetry, 17(4), 554-559(2006).
18 Brands, K.M.J., Payack, J.F., Rosen, J.D., Nelson, T.D., Candelario, A., Huffman, M.A., Zhao, M.M., Jing, L., Craig, B., Song, Z., Tschaen, D.M., Hansen, K., Devine, P.N., Pye, D.J., Rossen, K., Dormer, P.G., Reamer, R.A., Welch, C.J., Mathre, D.J., Tsou, N.N., Mcnamara, J.M., Reider, P.J., “Efficient synthesis of NK1 receptor antagonist aprepitant using a crystallization-induced diastereoselective transformation”, J. Am. Chem. Soc., 125(8), 2129-2135(2003).
19 Zhang, F., Wang, M., Jiang, S., Liu, C.M., Wu, X.M., Tao, J., Wei, J.B., “Asymmetric synthesis of(S)-3,5-bis(trifluoromethyl) acetophenol by yeast in organic solvent system”, Pharm. Biotechnol., 16(1), 411-414(2007).(in Chinese)
20 Xue, Y., Zhang, F., Wang, M., Li, J.Q., “Biosynthesis of(S)-3,5bis(trifluoromethyl)phenethyl alcohol with immobilized cells in biphasic system”, Chin. J. Pharm., 40(8), 573-577(2009).(in Chinese)
21 Wang, P., Sun, L. M., He, J. Y., “Medium optimization for enhanced production of carbonyl reductase by Candida tropicalis 104 by response surface methodology”, Chin. J. Biotech., 25(6), 863-868(2009).(in Chinese)
22 Wang, P., He, J.Y., Sun, L.M., Tang, J., “Method for producing(S)-1-(3,5-bis(trifluoromethyl)phenyl)ethanol through bioconversion by Candida tropicalis 104”, CN Pat., 10096423(2009).(in Chinese)
23 Stewart, J.D., “Organic transformations catalyzed by engineered yeast cells and related systems”, Curr. Opin. Biotechnol., 11(4), 363-368(2000).
24 Zhang, B.L., Pionnier, S., “Cofactor recycling mechanism in asymmetric biocatalytic reduction of carbonyl compounds mediated by yeast: which is the efficient electron donor?”, Chem. Eur. J., 9(15), 3604-3610(2003).
25 Johanson, T., Katz, M., Gorwa-Grauslund, M.F., “Strain engineering for stereoselective bioreduction of dicarbonyl compounds by yeast reductases”, FEMS Yeast Res., 5(6-7), 513-525(2005).

[1]	Chunlei Ren, Tao Wang, Xiaoyan Zhang, Jiang Pan, Jianhe Xu, Yunpeng Bai. Asymmetric bioreduction of γ- and δ-keto acids by native carbonyl reductases from Saccharomyces cerevisiae[J]. 中国化学工程学报, 2021, 29(1): 305-310.
[2]	Yao Li, Xiaoyang Ou, Zewang Guo, Minhua Zong, Wenyong Lou. Using multiple site-directed modification of epoxide hydrolase to significantly improve its enantioselectivity in hydrolysis of rac-glycidyl phenyl ether[J]. 中国化学工程学报, 2020, 28(8): 2181-2189.
[3]	Han Zu, Hui Zhang, Anwen Fan, Jie Gu, Yao Nie, Pengjie Luo, Yan Xu. Highly efficient synthesis of (R)-1,3-butanediol via anti-Prelog reduction of 4-hydroxy-2-butanone with absolute stereoselectivity by a newly isolated Pichia kudriavzevii[J]. 中国化学工程学报, 2020, 28(8): 2160-2166.
[4]	常煦, 杨忠华, 曾嵘, 杨改, 颜家保. Production of Chiral Aromatic Alcohol by Asymmetric Reduction with Vegetable Catalyst[J]. , 2010, 18(6): 1029-1033.
[5]	肖美添, 叶静, 张亚武, 黄雅燕. Reaction Characteristics of Asymmetric Synthesis of (2S,5S)-2,5-Hexanediol Catalyzed with Baker’s Yeast Number 6[J]. , 2009, 17(3): 493-499.
[6]	XIAOMeitian(肖美添),HUANGYayan(黄雅燕),MENGChun(孟春)andGUOYanghao(郭养浩). Kinetics of Asymmetric Reduction of Phenylglyoxylic Acid to R-(－)-Mandelic Acid by Saccharomyces Cerevisiae FD11b[J]. , 2006, 14(1): 73-80.

Asymmetric Bioreduction of 3,5-Bis(trifluoromethyl) Acetophenone to Its Corresponding Alcohol by Candida tropicalis

Asymmetric Bioreduction of 3,5-Bis(trifluoromethyl) Acetophenone to Its Corresponding Alcohol by Candida tropicalis

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

本文评价