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

This paper reports procedures for the straightforward in situ generation of Fmoc-amino acid chlorides using bis(trichloromethyl)carbonate (BTC) and th eir utilization for difficult couplings during solid-phase peptide synthesi s. The BTC-mediated coupling of all Fmoc-protected proteinogenic amino acid s to a large variety of N-alkylated amino acid-peptidyl-resin was studied. The majority of the couplings proceeded with quantitative conversion and wi thout racemization. The utilization of ETC-mediated coupling for facile sol id-phase synthesis of backbone cyclic peptides is presented.