Synthesis of amide-type fluoroalkene dipeptide isosteres by an intramolecular redox reaction

J Org Chem. 2009 May 1;74(9):3278-85. doi: 10.1021/jo900135t.

Abstract

We previously achieved NHC-mediated preparation of ester-type fluoroalkene dipeptide isosteres (ES-FADIs, 4) by an intramolecular redox reaction. In the present study, a cyanide ion-mediated reaction was successfully applied to the conversions of gamma,gamma-difluoro-alpha,beta-enoylsilane 1 or 2 to amide-type fluoroalkene isosteres (AM-FADIs, 5 or 6). The use of catalytic cyanide ion allowed synthesis of chiral auxiliary incorporated FADI 15b which was then subjected to a diastereoselective alpha-alkylation reaction to yield alpha-substituted FADIs 17. Furthermore, the presented amidation protocol was used for straightforward incorporation of FADI into peptidyl resin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry*
  • Alkylation
  • Amides / chemistry*
  • Cyanides / chemistry
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Oxidation-Reduction
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Alkenes
  • Amides
  • Cyanides
  • Dipeptides