Efficient solution phase synthesis of [l‐(β‐mercapto‐β, β‐cyclopentamethylenepropionic acid)‐ 2‐(O‐ethyl‐d‐tyrosine)‐4‐valine‐9‐desglycine]arginine vasopressin

Publisher Website
Google Scholar
Abstract
A convergent synthesis of the peptide [1‐(β‐mercapto‐β,β‐cyclopentamethylenepropionic acid)‐2‐(O‐ethyl‐d‐tyrosine)‐4‐valine‐9‐desglycine]arginine vasopressin (1), based on the classical solution phase method, was developed. The molecule is assembled by a 3 + 4 coupling via the amide method; then the disulfide bridge is installed by iodine treatment of the bis‐acetamidomethyl protected thiols, and the terminal arginine amide added by a 7 + 1 coupling. The method (see Scheme 1) has been used to prepare gram quantities of 1 in more than 98% purity and in 13% yield (based on tetrapeptide intermediate 13) after a single stage purification. The method appears to be particularly suitable for the large scale preparation of 1 and other vasopressin congeners. A novel, albeit low level, transfer of acetamidomethyl group from the sulfur of cysteine to the asparagine amide side‐chain was detected following hydrogen chloride treatment of Boc‐containing intermediates.
Keywords

This publication has 16 references indexed in Scilit: