The Controlled Synthesis of Peptides in Aqueous Medium. The Preparation and Use of Novel α-Amino Acid N-Carboxyanhydrides

Abstract

The preparation of the crystalline α-amino acid N-carboxyanhydrides (Leuchs' anhydrides, NCA's) of the following amino acids is described: aspartic acid, asparagine, glutamine, O-trimethylsilylserine, O-trimethyl-silylthreonine, O-trichloroacetylserine, histidine hydrobromide, ϵ-N-tert-butyloxycarbonyllysine, O-(2-tetra-hydropyranyl)tyrosine. All of these NCA's, except those of histidine and of O-trichloroacetylserine, were shown to be useful in the controlled synthesis of peptides in aqueous medium. The advantages of the use in peptide chemistry of the NCA's of aspartic and glutamic acids, unprotected on the ω-carboxy group, are discussed. The novel, noncrystalline NCA of arginine hydrobromide was found useful in peptide synthesis. New procedures are given for the preparation of the known NCA's of serine, threonine, and O-acetyltyrosine. The process for the preparation of the NCA of ϵ-N-tert-butyloxycarbonylIysine should have general utility for the preparation of NCA's with acid-labile blocking groups. The mechanism of the hydrolytic rearrangement of the NCA's of serine, threonine, and histidine is discussed. © 1971, American Chemical Society. All rights reserved.