Synthesis of psiSCH_2-, psiSOCH_2-, and psiSO_2CH_2-Peptide Isosters

摘要

Though chi-aminophosphonamides (A) are stable building blocks in peptides and serve as analogues of tetrahedrai intermediates of peptide cleavage, the sulfur derivatives B could not be synthesized until now. despite many attempts. The instability of 2-aminosulfonamides can be explained by an elimination, as indicated in Scheme l (cf. formation and cleavage of hydro-gensulfite adducts of aldehydes and ketones). Obviously, this complication is not present in the beta-aminosulfonic acid derivatives C. We have now prepared new types of sulfur-containing peptide isosteres of type D (n = 0, 1, 2), in which a subtle interplay between the donor ability of the RCONH group and the nucleofugality of the SO_nCH_2 group determines the stability (see D and Tablein Scheme 1).