Total synthesis of urogastrone (human epidermal growth factor, h-EGF). Part 2. Synthesis of urogastrone having the structure proposed for the natural compound

Abstract

Deprotection of the fully protected urogastrone was carried out by a two-step deprotection strategy. In the first step the protecting groups of all side-chain functional groups except for the cysteine thiol were removed by treatment with HF and the resulting (S-Acm)₆-urogastrone was purified by ion-exchange chromatography prior to the disulphide bond formation. In the second step the six Acm groups of the purified (S-Acm)₆-urogastrone were removed by Hg(OAc)₂. After formation of disulphide bonds by air oxidation, the synthetic urogastrone was purified by ion-exchange chromatography and gel filtration. The structure of the synthetic urogastrone was further characterized by amino acid analysis, tryptic peptide mapping, thermolytic peptide mapping, and fast atom bombardment mass spectroscopy.