Selektiv S‐geschützte Cysteinpeptide. IV. Zur Synthese von Cysteinpeptiden unter Verwendung der S‐Ethylthio‐Schutzgruppe. II

Abstract

Selectively S‐Protected Cysteine Peptides. IV Synthesis of Cysteine Peptides Using the S‐Ethylthio Protecting Group. II Studying the problems of the selective sulphur protection in cysteine peptides, a model octapeptide from the sheep insulin A‐chain was prepared by conventional synthesis using the S‐ethylthio and the S‐diphenylmethyl group. As consequence of the small acid stability of S‐ethylthio protected cysteine peptides, the corresponding compounds were synthesized using the strong acid labile 2‐(p‐biphenylyl)‐iso‐propyloxycarbonyl(Bpoc) and the 2‐phenyl‐iso‐propyloxycarbonyl(Ppoc) amino protecting group, respectively. Therefore a new synthesis of N‐protected S‐alkylthio cysteine derivatives 5 via N‐unprotected compounds 4 was developed starting from S‐guanylthio cysteine dihydrochloride 3. The synthesis of the octapeptide Boc‐Cys(SEt)‐Cys(Dpm)‐Ala‐Gly‐Val‐Cys(SEt)‐Ala‐Leu‐OBut 1 was carried out with the fragments Boc‐Cys(SEt)‐Cys(Dpm)‐Ala‐Gly‐OH and TFA · H‐Val‐Cys(SEt)‐Ala‐Leu‐OBut 12 by means of the DCCI/HOOBt coupling method. 12 was synthetisized step by step from the carboxyterminal end. The S‐ethylthio group was completely stable during all synthetic steps including the deprotection of the Nα‐Bpoc and Nα‐Ppoc group, respectively. The cyclocystine octapeptide 2, Boc‐Cys‐Cys(Dpm)‐Ala‐Gly‐Val‐Cys‐Ala‐Leu‐OBut, was produced by treatment of 1 with an excess of HSCH2CH2OH followed by oxidation with ICH2CH2I.