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Modulation of the properties of penicillin G acylase by acyl donor substrates during N-protection of amino compounds

Abstract:

The rates and yields in the synthesis of N-protected amino compounds catalyzed by penicillin G acylase are very different when using different protecting reagents, D- or L-mandelic acid methyl ester, or D- or L-phenylglycine methyl ester. L-mandelic acid methyl ester (L-MAME) gave the best adsorption of the nucleophile, the best transferase/hydrolase activity ratios, and the lowest rate of hydrolysis of the synthetic product when using several amino compounds (antibiotic nucleus, hydroxylamine, amino acids, and amino acid derivatives). Foe example, L-MAME gave synthetic yields up to 32-fold higher than D-phenylglycine for enzymic protection of tyrosinamide. Furthermore, N-protection of chiral amines by penicillin G acylase are extremely stereospecific; thus, optically pure L-mandelyl-L-amino acids were produced at high yields by protection of racemic mixtures of amino acids (alanine, phenylglycine, etc.) catalyzed by penicillin G acylase under very mild experimental conditions (aqueous media, neutral pH, and moderate temperature).