CONVENIENT HIGH-YIELDING GRAM SCALE SOLUTION SYNTHESIS OF METHIONINE-ENKEPHALIN

A simple, large-scale synthesis of a cytokine, methionine-enkephalin, Tyr-Cly-Gly-Phe-Mct, has been elaborated. Classical solution peptide c hemistry methods without protection of amino acid side-chain functions and 1+(2+2) segment condensation were used. A nine-step synthesis fro m commercial amino acid derivatives was developed with yields ranging from 86% to 99%, averaging 92%. The purity of all intermediates was fo und to be 99.0-100% by HPLC. The process has been used to prepare grea ter than 150 g quantities of the pentapeptide as a monohydrate of 100% purity. Hydantoin formation,vas observed during saponification of Boc -Tyr-Gly-Gly-Phe-Met-OMe and minimised.