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.
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.
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Acknowledgments
This work was financially supported by the Application Development Progam Chongqing Municipality (CSTC2013yykfa10017).
Supporting Information
Details of the microbial screening procedure.
Supplementary Table 1—Microorganisms screened for the reduction of 2 to (5)-1.
Supplementary Table 2—Morphological characterization, biochemical and physiological characteristics of Pseudomonas pseudoalcaligenes XW-40.
Supplementary Fig. 1—Neighbor-joining phylogenetic tree based on 16S rRNA gene sequences shows the relationship of Pseudomonas pseudoalcaligenes XW-40 and its related taxa.
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Wei, Y., Xia, S., He, C. et al. Highly enantioselective production of a chiral intermediate of sitagliptin by a novel isolate of Pseudomonas pseudoalcaligenes . Biotechnol Lett 38, 841–846 (2016). https://doi.org/10.1007/s10529-016-2051-1
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DOI: https://doi.org/10.1007/s10529-016-2051-1