ENZYMATIC ASYMMETRIC-SYNTHESIS OF ALPHA-AMINO-ACIDS - ENANTIOSELECTIVE CLEAVAGE OF 4-SUBSTITUTED OXAZOLIN-5-ONES AND THIAZOLIN-5-ONES

A general enzymatic asymmetric synthesis of L-alpha-amino acids has be en developed. This method entails the use of the Pseudomonas cepacia l ipase (P-30) to catalyze the enantioselective methanolysis of a variet y of 4-substituted 2-phenyloxazolin-5-one derivatives in a nonpolar or ganic solvent to furnish optically-active N-benzoyl-L-alpha-amino acid methyl esters (ee = 66-98%), which in turn is subjected to a protease -catalyzed kinetic resolution yielding enantiomerically-pure N-benzoyl -L-alpha-amino acids. This synergistic coupling of two enzymes allows the ready preparation of L-alpha-amino acids of high enantiopurity in yields greater than 50%, an inherent advantage over conventional resol ution procedures. Two proteases were found to catalyze the enantiosele ctive hydrolysis of a variety of 4-substituted 2-phenylthiazolin-5-one derivatives to give N-(thiobenzoyl)-L-alpha-amino acids of high optic al purity.