Enzymatic synthesis of c-terminal arylamides of amino acids and peptides

Nuijens, T., Cusan, C., Kruijtzer, J.A.W., Rijkers, D.T. S., Liskamp, R.M.J. and Quaedflieg, P.J.L.M. (2009) Enzymatic synthesis of c-terminal arylamides of amino acids and peptides. Journal of Organic Chemistry, 74(15), pp. 5145-5150. (doi: 10.1021/jo900634g)

Abstract

A mild and cost-efficient chemo-enzymatic method for the synthesis of C-terminal arylamides of amino 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 be obtained from the corresponding C-terminal carboxylic acids, methyl (Me) or benzyl (Bn) esters, in high 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 α-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 of the cysteine protease papain and the lipase Cal-B gave anilides in high yields. The chemo-enzymatic synthesis of arylamides proved to be completely free of racemization, in contrast to the state-of-the-art chemical methods.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert
• Authors: Nuijens, T., Cusan, C., Kruijtzer, J.A.W., Rijkers, D.T. S., Liskamp, R.M.J., and Quaedflieg, P.J.L.M.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Journal of Organic Chemistry
• Publisher: American Chemical Society
• ISSN: 0022-3263