Total synthesis of urogastrone (human epidermal growth factor, h-EGF). Part 1. Synthesis of the fully protected urogastrone

Abstract

The first total synthesis of urogastrone (h-EGF) has been achieved by the segment condensation method in solution applying the maximum protection strategy with a two-step deprotection procedure. The polypeptide chain was constructed from 10 small segments which were synthesized in a conventional fashion using Boc for the amino protecting group, Acm for the thiol protecting group, and Pac for the carboxy protecting group except for segments (48–53) and (1–5), which were protected with Bzl and Troc hydrazide, respectively. The larger fragment condensation reactions were successfully carried out by the WSCD-HOBt method and the azide method to obtain the fully protected tripentacosapeptide corresponding to the sequence of urogastrone.