SYNTHESIS OF PEPTIDES BY FRAGMENT CONDENSATION ON A SOLID SUPPORT

Abstract
A convenient scheme for the synthesis of 4,8‐disubstituted vasopressins has been designed and its usefulness evaluated in the preparation of one of the parent hormones, 8‐arginine‐vasopressin. The main feature of the scheme involves preparation of two protected tripeptide fragments, Z‐Cys(Bzl)‐Tyr(Bzl)‐Phe and Boc‐Asn(Mbh)‐Cys(Bzl)‐Pro which are incorporated in a synthesis on a solid support. Both tripeptides were prepared conventionally with the carboxyl groups protected as benzyl esters. The benzylester groups were removed by transesterification with 2‐dimethylaminoethanol and subsequent hydrolysis. To avoid racemization in the coupling step with the fragment containing a C‐terminal phenylalanine, N‐hydroxysuccinimide was added. After removal of the peptide from the resin, deprotection, oxidation and desalting, final purification was effected by ion‐exchange chromatography. Apart from the main product, which exhibited full pressor activity, only small amounts of impurities could be isolated.