In situ generation of Fmoc-amino acid chlorides using bis-(trichloromethyl) carbonate and its utilization for difficult couplings in solid-phase peptide synthesis

J Pept Res. 1999 May;53(5):507-17. doi: 10.1034/j.1399-3011.1999.00049.x.

Abstract

This paper reports procedures for the straightforward in situ generation of Fmoc-amino acid chlorides using bis-(trichloromethyl)carbonate (BTC) and their utilization for difficult couplings during solid-phase peptide synthesis. The BTC-mediated coupling of all Fmoc-protected proteinogenic amino acids to a large variety of N-alkylated amino acid-peptidyl-resin was studied. The majority of the couplings proceeded with quantitative conversion and without racemization. The utilization of BTC-mediated coupling for facile solid-phase synthesis of backbone cyclic peptides is presented.

MeSH terms

  • Alkylation
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Carboxylic Acids / chemistry
  • Chlorides / chemical synthesis
  • Fluorenes / chemical synthesis*
  • Fluorenes / chemistry
  • Peptides, Cyclic / chemical synthesis*
  • Phosgene / analogs & derivatives*
  • Phosgene / chemistry

Substances

  • Amino Acids
  • Carboxylic Acids
  • Chlorides
  • Fluorenes
  • N(alpha)-fluorenylmethyloxycarbonylamino acids
  • Peptides, Cyclic
  • Phosgene
  • bis(trichloromethyl) carbonate