The use of N-urethane-protected N-carboxyanhydrides (UNCAs) in amino acid and peptide synthesis

J Pept Sci. 1995 Mar-Apr;1(2):124-31. doi: 10.1002/psc.310010204.

Abstract

N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactive amino acid derivatives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected beta amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerically pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced [4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl malonate in the presence of sodium hydride to yield gamma-N-benzyloxycarbonylamino-beta-oxodicarboxyl esters followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodo]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Amino Alcohols / chemical synthesis
  • Amino Alcohols / chemistry
  • Anhydrides / chemistry
  • Indicators and Reagents
  • Methods
  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Urethane / chemistry

Substances

  • Amino Acids
  • Amino Alcohols
  • Anhydrides
  • Indicators and Reagents
  • Peptides
  • Urethane
  • statine