Integration of newly isolated biocatalyst and resin-based in situ product removal technique for the asymmetric synthesis of (R)-methyl mandelate.
The enantioselective reduction of methyl benzoylformate to (R)-methyl mandelate, an important pharmaceutical intermediate and a versatile resolving agent, was investigated in this study. After minimizing the reaction-specific constraints (constraints dependent on the nature of the substrate and product) by preliminary selection of the reaction parameters, an effective whole cell biocatalyst (Saccharomyces cerevisiae AS2.1392) was obtained by simple screening procedures. Under further optimized conditions, a product concentration of 103 mmol L(-1) could be attained within 5 h with a yield of 85.8% and an enantiometric excess of 95.4%, indicating S. cerevisiae AS2.1392 an efficient biocatalyst for the asymmetric synthesis of (R)-methyl mandelate. Furthermore, resin-based in situ product removal (ISPR) technique was applied to alleviate the substrate and product inhibition or toxicity to the whole cells. The integration of newly isolated biocatalyst and proper ISPR technique provides a practical route for the preparation of optically active pharmaceutical intermediates.
Guo
Jin-Ling
JL
Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, 214122 Wuxi, Jiangsu, China. guo3jin4ling5@yahoo.com.cn
Mu
Xiao-Qing
XQ
Xu
Yan
Y
D000042:Absorption; D002384:Catalysis; D006038:Glyoxylates / Q000737:chemistry / Q000378:metabolism*; D008333:Mandelic Acids / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000378:metabolism*; D012117:Resins, Synthetic / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D018511:Systems Integration
D006038:Glyoxylates; D008333:Mandelic Acids; D012117:Resins, Synthetic; C414090:methyl mandelate; C034307:4-methylbenzoylformic acid