Synthesis of optically active vicinal fluorohydrins by lipase-catalyzed deracemization

J Org Chem. 2002 May 3;67(9):3015-21. doi: 10.1021/jo016331r.

Abstract

Three microbial lipases have been used to deracemize trans-2-fluorocycloalkanols 2 both by hydrolysis of the corresponding acetates 3 or chloroacetates 4 and by esterification of the fluorohydrins 2 using vinyl acetate and vinyl chloroacetate, respectively. Pseudomonas cepacia lipase was the most selective for the six- and the seven-membered-ring compounds, while the lipase from Candida rugosa was most useful for the eight-membered-ring compounds. Both lipases transform the (R)-enantiomers preferentially. In contrast the lipase from Candida antarctica hydrolyzed the esters of trans-2-fluorocyclohexanol 2a and esterified the fluorohydrin itself with very low enantiopreference for the (R)-isomers. The seven- and the eight-membered ring esters and the corresponding fluorohydrins were also transformed with low, but reverse, enantioselectivity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Acetates / metabolism
  • Candida / enzymology
  • Catalysis
  • Circular Dichroism
  • Esterification
  • Hydrocarbons, Cyclic / chemical synthesis*
  • Hydrocarbons, Cyclic / metabolism*
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / metabolism*
  • Hydrolysis
  • Kinetics
  • Lipase / metabolism*
  • Molecular Structure
  • Pseudomonas / enzymology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Vinyl Compounds / chemistry
  • Vinyl Compounds / metabolism

Substances

  • Acetates
  • Hydrocarbons, Cyclic
  • Hydrocarbons, Fluorinated
  • Vinyl Compounds
  • Lipase