Preparation of oligomer‐free N^α‐Fmoc and N^α‐urethane amino acids

Abstract

A variety of N α ‐urethane blocked amino acids, in particular 9‐fluorenylmethyloxycarbonyl (Fmoc) derivatives, have been synthesized by utilizing intermediate O,N ‐ bis ‐trimethylsilyl‐amino acids, formed in situ by treating an amino acid with trimethylsilylchloride and a base in an aprotic solvent. The intermediate is then reacted with an acylating agent. A general procedure is given which eliminates the oligomerization side reactions normally observed in Schotten‐Baumann type methods. Protected amino acids obtained from this procedure are of high purity as judged by t.l.c, HPLC, ion exchange chromatography, and other physical parameters.