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α,α-Disubstituted α-amino acid amides were prepared in 17–86% chemical yield by the phase-transfer catalyzed alkylation of N-benzylidene α-H amino acid amides, followed by weak acidic hydrolysis of the Schiff bases.

The scope and limitations of the enzymatic resolution of α,α-disubstituted α-amino acid amides by an amino acid amidase from Mycobacterium neoaurum and of the corresponding ethyl esteis with Pig liver estetase (PLE) have been studied. Moderate enantiomeric excesses were obtained with PLE, with only a narrow substrate specificity. Mycobacterium neoaurum on the contrary yields a broad range of S-α,α-disubstituted α-amino acids 1 and the corresponding R-amides 2.

(S)-cyclohexylglycine (1) is prepared in high yield by hydrogenation of (S)-phenylglycine (2) using rhodium on carbon as the catalyst.

A new strategy for the biocatalytic resolution of (R,S)-phenylglycinonitrile, a crucial intermediate in the antibiotic industry, has been developed. While former techniques exploit nitrilases or combinations of nitrile hydratases and amidases, manipulating with nitrile functionality, the current approach is based on a highly efficient and enantioselective acylation of the α-amino group with phenylacetic acid catalyzed by a well known enzyme, penicillin acylase from E. coli, in slightly acidic aqueous medium. It is shown that since the condensation product is poorly soluble, removal of (S)-phenylglycinonitrile from the reaction sphere is almost complete and irreversible, favoring kinetics of the process and making high conversion possible. The proposed approach is characterized by high space-time yield and extends the scope of enzymatic synthesis in aqueous medium.