The application of methods developed mostly in this laboratory permitted the synthesis of the fully S,Nprotected heptapeptides N-carbobenzoxy-S-trityl-L-cysmethyl ester ( X X I I , Figure 3). For these syntheses, a variety of N -and S-protecting groups was used; this allowed selective removal of either the N-, or two of three S-protecting groups according to desired aims. Thus, selective removal of the two Strityl groups f r o m VIII and X and of the two S-benzoyl groups f r o m X X I I led to the formation of the corresponding dithiol compounds X X V , X X V I , and X X V I I . B y oxidation of these thiol compounds a disuljde bridge was established specijcally between two of the three cysteine residues incorporated in the above three heptapeptides. The corresponding oxidation products XXVIII, X X I X , and XXX are derivatives of the 6-12 sequence of the A chain of sheep insulin bearing the 6-11 intrachain bridge (Figure 1). Removal of the N-protecting groups f r o m the cyclic peptide esters X X I X and XXX aflorded the cyclic peptide ester hydrochlorides X X X I and X X X I I from which the remaining S-protecting group can be removed b y established methods. The significance of the above cyclic peptides as regards the problem of insulin synthesis is discussed, The possibility of an S+N acyl migration should be taken into account when using S-acylcysteines in peptide synthesis. It was proved that such a migration does not take place, at least in detectable extent, during the course of the synthesis of the S,N-protected heptapeptide X X I I .
IntroductionIn previous communications from this l a b o r a t~r y~-~ N-protected S-trityl-, S-diphenylmethyl-, and S-acyl-L-
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