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)

Abstract

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
Volume64
Issue number1-2
DOIs
Publication statusPublished - 2010 Jun

Fingerprint

Biocatalysis
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enantiomers
Lipase
Candida
Isomers
Acetates
Hydrolysis
Kinetics
Temperature
Enantioselectivity
Lipases
Reaction rates
Candida antarctica lipase B
Recovery
Substrates

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Bioengineering
  • Catalysis
  • Process Chemistry and Technology

Cite this

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title = "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",
abstract = "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.",
keywords = "Asymmetric reduction, Hydrolysis, Kinetic resolution, Lipase, Statin, Yeast",
author = "Maki Sakamoto and Manabu Hamada and Toshinori Higashi and Mitsuru Shoji and Takeshi Sugai",
year = "2010",
month = "6",
doi = "10.1016/j.molcatb.2010.02.008",
language = "English",
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pages = "96--100",
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T1 - 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

AU - Sakamoto, Maki

AU - Hamada, Manabu

AU - Higashi, Toshinori

AU - Shoji, Mitsuru

AU - Sugai, Takeshi

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

KW - Asymmetric reduction

KW - Hydrolysis

KW - Kinetic resolution

KW - Lipase

KW - Statin

KW - Yeast

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