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)

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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

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