Selectivity of biohydroxylation with Beauveria bassiana of trans-2-fluorocycloalkyl N-phenylcarbamates

J Org Chem. 2002 May 3;67(9):3022-8. doi: 10.1021/jo016332j.

Abstract

Biohydroxylation with Beauveria bassiana of racemates and the pure enantiomers of trans-2-fluorocyclohexyl- 3 and trans-2-fluorocycloheptyl N-phenylcarbamates 6 were investigated and compared with results found for the corresponding nonfluorinated parent compounds. In all cases, mixtures of diastereomeric products hydroxylated in the 4-position were isolated, besides products of p-hydroxylation of the aromatic ring and succeeding compounds derived from these primary reaction products. The regioselectivity of hydroxylation by this fungus is not changed by a single fluorine substituent attached closely to the electron-rich anchoring group in the trans-2-position. There is a different influence on the diastereoselectivity of hydroxylation depending on the absolute configuration of the fluorinated substrates. While the transformation of the (S,S)-2-fluorocycloalkyl N-phenylcarbamates is not diastereoselective giving almost 1:1 mixtures of cis- and trans-4-hydroxyl compounds, the corresponding reactions of the (R,R)-isomers led preferentially to the products trans-hydroxylated in the 4-position. The transformation of the racemic fluorinated six-membered N-phenylcarbamate 3 led to products having a very small enantiomeric excess. The fluorine substituent slightly increased the enantioselectivity of transformation of the racemic seven-membered substrate 6 compared to the C(s)()-symmetric nonfluorinated carbamate. Thus, the fluorine substituent in the trans-2-position in these examples did not change the regioselectivity but rather influenced the stereochemistry of biotransformation, depending on the absolute configuration of the substrate and ring size.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotransformation
  • Carbamates / chemistry*
  • Carbamates / metabolism
  • Catalysis
  • Fungi / metabolism*
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / metabolism*
  • Hydroxylation
  • Lipase / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Pseudomonas / enzymology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Carbamates
  • Hydrocarbons, Fluorinated
  • Lipase