Enzymatic Synthesis of C-Terminal Arylamides ofAmino Acids and Peptides

摘要

A mild and cost-efficient chemo-enzymatic method for the synthesis of C-terminal arylamides ofamino acid and peptides is described. Using the industrial serine protease Alcalase under near-anhydrous conditions, C-terminal arylamides of N-Cbz-protected amino acids and peptides could beobtained from the corresponding C-terminal carboxylic acids, methyl (Me) or benzyl (Bn) esters, inhigh chemical and enantio- and diastereomeric purities. Yields ranged between 50% and 95%depending on the size of the aryl substituents and the presence of electron-withdrawing substituents.Complete a-C-terminal selectivity could be obtained even in the presence of various unprotected side-chain functionalities such as β/γ-carboxyl, hydroxyl, and guanidino groups. In addition, the use ofthe cysteine protease papain and the lipase Cal-B gave anilides in high yields. The chemo-enzymaticsynthesis of arylamides proved to be completely free of racemization, in contrast to the state-of-the-art chemical methods.