Highly efficient chemoenzymatic synthesis of methyl (R)-o-chloromandelate, a key intermediate for clopidogrel, via asymmetric reduction with recombinant Escherichia coli

Tadashi Ema, Sayaka Ide, Nobuyasu Okita, Takashi Sakai

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82 Citations (Scopus)

Abstract

Methyl (R)-o-chloromandelate [(R)-1], which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o-chlorobenzoylformate (2) with recombinant Escherichia coli overproducing a versatile carbonyl reductase. A remarkable temperature effect on productivity was observed in the whole-cell reduction of 2, and the optimum productivity as high as 178 g/L was attained at 20°C on a 2-g scale (1.0 M). The optimized reaction could be scaled up easily to transform 20 g of 2 in 100 mL of buffer. Three synthetic methods for 2 are compared.

Original languageEnglish
Pages (from-to)2039-2044
Number of pages6
JournalAdvanced Synthesis and Catalysis
Volume350
Issue number13
DOIs
Publication statusPublished - Sep 5 2008

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Keywords

  • Asymmetric catalysis
  • Biotransformations
  • Chemoenzymatic synthesis
  • Enzyme catalysis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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