Study of the Synthesis of Histidine Peptides. II. Use of Nim-Tosylhistidine Derivatives in Conventional Solution Synthesis of Peptides

Abstract

Abstract His–Gly and Ala–His–Gly were synthesized by the conventional solution methods using various Nα-protected-Nim-tosyl-l-histidines as the key intermediates, and handling conditions of these His(Tos)-derivatives were examined. During treatment of an Nps-peptide with HF, the formation of a strongly photosensitive by-product was observed when anisole alone was used as the scavenger, however the side reaction was completely suppressed when skatole was added to the reaction mixture. In order to evaluate the usefulness of these His(Tos)-derivatives in general peptide synthesis, TRH and LH–RH were synthesized, and both products were obtained in pure form without any difficulty. Thus, it can be emphasized that the use of these His(Tos)-derivatives is efficient and convenient for introducing His-residues into peptides even in solution procedures.