title: Highly enantioselective production of a chiral intermediate of sitagliptin by a novel isolate of Pseudomonas pseudoalcaligenes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, 400065, People's Republic of China.
authors: Yanchan
authors: Y
authors: Wei
authors: College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, 400065, People's Republic of China. xiasw@cqupt.edu.cn.
authors: Shiwen
authors: S
authors: Xia
authors: College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, 400065, People's Republic of China.
authors: Conglin
authors: C
authors: He
authors: College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, 400065, People's Republic of China.
authors: Wenjuan
authors: W
authors: Xiong
authors: College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, 400065, People's Republic of China.
authors: Hongmei
authors: H
authors: Xu
mesh_terms: D010084:Oxidation-Reduction; D044205:Pseudomonas pseudoalcaligenes / Q000378:metabolism*; D000068900:Sitagliptin Phosphate / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000068900:Sitagliptin Phosphate
keywords: Carbonyl reductase; Chiral alcohol; Pseudomonas pseudoalcaligenes; Sitagliptin; Whole cell-bioreduction