Anhydrides as acylating agents in the enzymatic resolution of an intermediate of (-)-Paroxetine

J Org Chem. 2003 Apr 18;68(8):3333-6. doi: 10.1021/jo034120b.

Abstract

A new chemoenzymatic method for the preparation of an intermediate of (-)-Paroxetine is reported. Cyclic anhydrides are used as acylating agents in the lipase-catalyzed esterification of trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine in organic solvents. The best enantioselectivities are obtained with two different lipases from Candida antarctica. These two lipases show opposite stereochemical preference in these processes, so that both enantiomers can be obtained in their optically pure forms. The (3S,4R) isomer is an intermediate for the synthesis of (-)-Paroxetine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Anhydrides / chemistry
  • Anhydrides / metabolism*
  • Candida / enzymology*
  • Catalysis
  • Esterification
  • Indicators and Reagents
  • Lipase / metabolism*
  • Paroxetine / analogs & derivatives
  • Paroxetine / chemical synthesis*
  • Piperidines / chemistry
  • Solvents
  • Stereoisomerism

Substances

  • 4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine
  • Anhydrides
  • Indicators and Reagents
  • Piperidines
  • Solvents
  • Paroxetine
  • Lipase