Highly enantioselective production of a chiral intermediate of sitagliptin by a novel isolate of Pseudomonas pseudoalcaligenes

作者：Wei, Yanchan; Xia, Shiwen^*; He, Conglin; Xiong, Wenjuan; Xu, Hongmei

来源：Biotechnology Letters, 2016, 38(5): 841-846.

DOI：10.1007/s10529-016-2051-1

• Chiral alcohol
• Carbonyl reductase
• Pseudomonas pseudoalcaligenes
• Sitagliptin
• Whole cell-bioreduction

Objective To produce (S)-3-hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1-one (S)-1 from 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-one (2) by microbial bioreduction. @@@ Results A new isolate of Pseudomonas pseudoalcaligenes reduced enantioselectively prochiral ketone 2 to chiral alcohol (S)-1. Whole cells of the bacterium were tolerant towards 20 % (v/v) DMSO and 10 g 2/l. Under the optimal conditions, the preparative-scale bioreduction yielded (S)-1 at 90 % yield and > 99 % ee. Cells could be re-used with the yield and ee of product being 45 % and > 99 %, respectively, after five cycles. @@@ Conclusion Bioreduction using whole cells of P. pseudoalcaligenes is an attractive approach to produce (S)-1, as a chiral intermediate of the anti-diabetic drug, sitagliptin.

• 出版日期2016-5
• 单位重庆邮电大学