Precursors thiolysis

In this approach an orthogonal S-protection consisting of the acid-labile Mob and the Acm group was selected. Free thiol peptides were prepared by acid treatment of the precursors and activated with di(2-pyridyl) disulfide to afford the 5-SPy derivatives which served for the preparation of the two heterodimers 60 and 62 via thiolysis with a second cysteine peptide. In both heterodimers 60 and 62 the Acm group was cleaved with silver(I) trifluoroacetate in TFA to generate the mercaptide. Following gel filtration in acidic media the free thiol from 62 was activated as the S-SPy derivative 63 and subsequent thiolysis with the second heterodimer 61 in the free thiol form produced the heterotetramer 64. 

In the acid-catalyzed thiolysis of nitriles (73) HaS is commonly replaced by appropriate precursors or equivalents. Thus, thioacids, RCOSH, have been used together with HC1 or SnCU. Thioacetamide (77) is a very convenient source of HaS as shown in equation (36), an equilibrium is established which is shifted to the right, if the liberated MeCN is removed by distillation. Alternative sources of HaS are di-thiophosphoric, HSP(=S) (OR)a with R = Et or Pr, " or phosphinodithioic acid derivatives, HSPPha(= S). ° The last mentioned approach allows the elegant synthesis of a-hydroxythioamides (78) in Scheme 11. ... 

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