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

Abstract

α-Azido carboxylic acids have recently emerged as versatile N-protected equivalents for α-amino acids, especially valuable when the sterically hindered C^α-dialkylated α-amino acids have to be incorporated. Unsymmetrically substituted C^α-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.

19

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.