Zhejiang Yongtai Technology Co., Ltd.

Zhejiang University

Zhejiang Yongtai Pharmaceutical Co., Ltd.

Renbao He

Lei Wang

Yuguo Zheng

Hongming Shao

Yizhong Jin

Feng Zhang

Zhiqiang Liu

Xiaojian Zhang

Dongxu Jia

Yingmei Wang

Jiaohua Lin

Feng Cheng

Yingshu Wang

The present invention discloses a transaminase mutant and application thereof in preparation of sitagliptin intermediates, the transaminase mutant is obtained by substitution of tyrosine with proline at position 74, substitution of glutamic acid with aspartic acid at position 228, substitution of leucine with alanine at position 254 and substitution of methionine with threonine at position 290 of the amino acid sequence shown in SEQ ID NO: 2. The present invention uses wet cells or a purified transaminase as a biocatalyst and a sitagliptin precursor ketone or a prochiral carbonyl compound as a substrate to prepare a sitagliptin intermediate or a sitagliptin ester intermediate; the total yield of the method reaches about 82%, and e.e. value of the product reaches 99%.

Transaminase mutant and application thereof in preparation of sitagliptin intermediates

The present invention relates to a method for synthesizing a compound of 3-(difluoromethyl)-1-methyl-1h-pyrazole-4-carboxylic acid, wherein including the steps of:   

Method for synthesizing 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid and intermediates thereof

Provided are a preparation method for synthesizing a pyrazolecarboxylic acid derivative of the following formula (I), which is suitable for industrial production, and an intermediate as shown by the following formula (II). The method is high in reaction yield in each step, low in waste gas and waste water and low in cost, and requires no special reaction equipment. 

Method for preparing pyrazolecarboxylic acid derivative, and intermediate thereof

Growing community of inventors

Zhejiang, China

Renbao He