Elaboration on the access to (S)-4-(4-methylbenzyl)oxy-3-hydroxybutanenitrile, a key intermediate for statins, by combining the kinetic resolution of racemate and the recycle of undesired enantiomer

Maki Sakamoto, Manabu Hamada, Toshinori Higashi, Mitsuru Shoji, Takeshi Sugai

Research output: Contribution to journalArticle

6 Citations (Scopus)


High enantioselectivity (E 94) was observed in Candida antarctica lipase B-catalyzed hydrolysis of the corresponding acetate of racemic title compound. The reaction rate of the slow (S)-isomer was effectively suppressed by lowering the reaction temperature from 25°C to 5°C, to allow a five times increase of the enantioselectivity. The ee of the (S)-isomer, reached 97.8% at the reasonable conversion (52%) as the unreacted recovery, and the repetition of the enzymatic reaction provided pure enantiomer. The undesired (R)-isomer was oxidized with IBX and reduced with whole-cell biocatalysis with Candida floricola JCM 9439 to (S)-isomer (63.2% ee), which serves as the enantiomerically enriched substrate for further lipase-catalyzed resolution. The combination of total processes provided over 50% yield of the pure (S)-isomer, exceeding the theoretical limit for the enantiomeric resolution of racemate.

Original languageEnglish
Pages (from-to)96-100
Number of pages5
JournalJournal of Molecular Catalysis B: Enzymatic
Issue number1-2
Publication statusPublished - 2010 Jun 1



  • Asymmetric reduction
  • Hydrolysis
  • Kinetic resolution
  • Lipase
  • Statin
  • Yeast

ASJC Scopus subject areas

  • Catalysis
  • Bioengineering
  • Biochemistry
  • Process Chemistry and Technology

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