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

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.