Kupplung von Peptiden mit C‐terminalen α,α‐disubstituierten α ‐ Aminosäuren via Oxazol‐5(4H)‐one

Peptide‐Bond Formation with C‐Terminal α,α‐Disubstituted α ‐ Amino Acids via Intermediate Oxazol‐5(4H)‐ones The formation of peptide bonds between dipeptides 4 containing a C‐terminalα,α‐disubstituted α‐amino acid and ethyl p‐aminobenzoate (5) using DCC as coupling reagent proceeds via 4,4‐disubstituted oxazol‐5(4H)‐ones 7 as intermediates (Scheme 3). The reaction yielding tripeptides 6 (Table 2) is catalyzed efficiently by camphor‐10‐sulfonic acid (Table 1). The main problem of this coupling reaction is the epimerization of the nonterminal amino acid in 4 via a mechanism shown in Scheme 1. CSA catalysis at 0° suppresses completely this troublesome side reaction. For the coupling of Z‐Val‐Aib‐OH (11) and Fmoc‐Pro‐Aib‐OH (14) with H‐Gly‐OBu1 (12) and H‐Ala‐Aib‐NMe2 (15), respectively, the best results have been obtained using DCC in the presence of ZnCl2 (Table 3).