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

Abstract

Peptide‐Bond Formation with C‐Terminal α,α‐Disubstituted α ‐ Amino Acids via Intermediate Oxazol‐5(4 H )‐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(4 H )‐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‐OBu 1 ( 12 ) and H‐Ala‐Aib‐NMe 2 ( 15 ), respectively, the best results have been obtained using DCC in the presence of ZnCl 2 ( Table 3 ).