Analogues of key precursors of aspartyl protease inhibitors: synthesis of trifluoromethyl amino epoxides

J Org Chem. 2005 Jan 21;70(2):699-702. doi: 10.1021/jo0485233.

Abstract

The synthesis of the title compound is described through original and tailored synthetic protocols. The addition of vinylmagnesium bromide to CF(3)-N-aryl and N-alkyl aldimines was efficient and did not require an activating N-substituent. The resultant CF3-allylamines were converted in an efficient and completely stereoselective route to syn CF3-epoxides 3 via formation of bromhydrins 8. The same sequence performed from the aldimine substituted with the methyl ether of the (R)-phenylglycinol provided the homochiral (R,R)-amino epoxide (de >98%). This study has allowed access to the novel racemic and homochiral trifluoromethyl beta-amino epoxides, analogues of key precursors of various HIV protease inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis*
  • Amines / chemistry
  • Amines / pharmacology
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Epoxy Compounds / chemical synthesis*
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology
  • Molecular Structure
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • Stereoisomerism

Substances

  • Amines
  • Enzyme Inhibitors
  • Epoxy Compounds
  • Prodrugs
  • Aspartic Acid Endopeptidases