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

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

• BIOTECHNOLOGY AND BIOENGINEERING • Previous Articles Next Articles

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:2012-04-24 Published:2011-12-28
Supported by:
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

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

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)

Abstract

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

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

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.

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.

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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

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