ИСТИНА

Penicillin acylase from Escherichia coli and its mutants stabilized to inactivation in alkaline medium and by high substrate concentrations have been used for preparative stereoselective synthesis of substituted and unsubstituted 2-hydroxyacyl derivatives of alpha-amino acids which then after activation of their carboxyl group by N,N’-dicyclohexylcarbodiimide were subjected to intramolecular cyclization to produce corresponding 2,5-diketomorpholines. Biocatalytic acylation in aqueous alkaline medium was very effective: for example at pH 9.5 acylation of 0.1 M DL-phenylalanine by 0.2 M (R)-mandelamide was 99% (yield calculated per amount of L-enantiomer of amino acid, synthesis/hydrolysis ratio 35). Due to the high stereoselectivity of enzyme to nucleophile (E ≈ 1000) N-(R)-mandelyl-(S)-phenylalanine (e.e. 99.9%) was produced. Using this methodology different cyclodidepsipeptides were synthesized with a good overall yield.