Chemoenzymatic approaches to the synthesis of the (1S,2R)-isomer of benzyl 2-hydroxycyclohexanecarboxylate

Ryuji Tsunekawa, Kengo Hanaya, Shuhei Higashibayashi, Mitsuru Shoji, Takeshi Sugai

Research output: Contribution to journalArticle

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Abstract

We examined ten strains of cultured whole-cell yeasts for the asymmetric reduction of commercially available ethyl 2-oxocyclohexanecarboxylate, and found that the (1S,2S)-stereoisomer of ethyl 2-hydroxycyclohexanecarboxylate was the major stereoisomer produced by Williopsis californica JCM 3600. The ethyl group of the ester was then substituted with a benzyl group with low volatility and increased hydrophobicity to facilitate the isolation of the expected product. Incubation with W. californica furnished benzyl (1S,2S)-2-hydroxycyclohexanecarboxylate (>99.9% ee) in 51.0% yield together with its (1R,2S)-isomer (>99.9% ee) in 35.4% yield. Upon treatment of the same substrate bearing the benzyl ester with a screening kit of purified overexpressed carbonyl reductases (Daicel Chiralscreen® OH), two enzymes (E031, E078) furnished the (1R,2S)-isomer as the major product. With another enzyme (E007), the (1S,2R)-isomer was obtained, but its ee was very low (25.6%). The highly enantiomerically enriched (1S,2S)-isomer obtained by W. californica was transformed to the (1S,2R)-isomer (>99.9% ee), whose availability until now has been low, in 43.3% yield over two steps involving tosylation and subsequent inversive attack with tetrabutylammonium nitrite.

Original languageEnglish
Pages (from-to)84-89
Number of pages6
JournalMolecular Catalysis
Volume444
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Isomers
isomers
synthesis
Stereoisomerism
enzymes
esters
Esters
Bearings (structural)
Enzymes
Alcohol Oxidoreductases
kits
volatility
nitrites
yeast
Hydrophobicity
products
hydrophobicity
Nitrites
cultured cells
Yeast

Keywords

  • Carbonyl reductase
  • Cyclic β-oxoester
  • Reduction
  • Whole-cell yeast biocatalyst

ASJC Scopus subject areas

  • Catalysis
  • Process Chemistry and Technology
  • Physical and Theoretical Chemistry

Cite this

Chemoenzymatic approaches to the synthesis of the (1S,2R)-isomer of benzyl 2-hydroxycyclohexanecarboxylate. / Tsunekawa, Ryuji; Hanaya, Kengo; Higashibayashi, Shuhei; Shoji, Mitsuru; Sugai, Takeshi.

In: Molecular Catalysis, Vol. 444, 01.01.2018, p. 84-89.

Research output: Contribution to journalArticle

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