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Synthesis 2005(2): 272-278  
DOI: 10.1055/s-2004-834947
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Enzymatic Resolution of Cα-Dialkylated α-Azido Carbox­amides: New Enantiopure α-Azido Acids as Building Blocks in Peptide Synthesis­

Micha Josta,, Theo Sonkeb, Bernard Kapteinb, Quirinus B. Broxtermanb, Norbert Sewald*a
a University of Bielefeld, Department of Chemistry, Organic and Bioorganic Chemistry, PO Box 100131, 33501 Bielefeld, Germany
Fax: +49(521)1068094; e-Mail: norbert.sewald@uni-bielefeld.de;
b DSM Research, Life Sciences-Advanced Synthesis & Catalysis, PO Box 18, 6160 MD Geleen, The Netherlands
Further Information

Publication History

Received 11 August 2004
Publication Date:
03 December 2004 (online)

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Abstract

α-Azido carboxylic acids have recently emerged as versatile N-protected equivalents for α-amino acids, especially valuable when the sterically hindered Cα-dialkylated α-amino acids have to be incorporated. Unsymmetrically substituted Cα-dialkylated α-azido carboxylic acids can be obtained in enantiomerically pure form by enzymatic resolution of α-azido carboxamides. A l-amidase from Ochrobactrum anthropi NCIMB 40321 accepts 2-azido-2,4-dimethylpentanamide as the substrate and provides both the corresponding S-configured α-azido carboxylic acid and the R-configured α-azido carboxamide in excellent enantiomeric purity. The former is a valuable synthetic precursor of α-methylleucine [(α-Me)Leu] in peptide synthesis, as demonstrated by the successful synthesis of a (α-Me)Leu containing efrapeptin C analogue.

Key words

azides - bioorganic chemistry - enantiomeric resolution - enzymes - peptides

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1

Present address: Università di Padova, Dipartimento di Scienze Chimiche, 35131 Padova, Italy.

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Sonke, T.; Ernste, S.; Tandler, R. F.; Kaptein, B.; Peeters, W. P. H.; van Assema, F. B. J.; Wubbolts, M. G.; Schoemaker, H. E. An l-Selective Amidase with Extremely Broad Substrate Specificity from Ochrobactrum anthropi NCIMB 40321, submitted.