Process for the preparation of acylated amino acid esters and resolving racemic mixtures of amino acid esters by enzyme-catalysed acylation

摘要

Production of acylated amino acid esters comprises acylating an amino acid ester with a carboxylic acid ester, which carries a halo, N, O or S atom in the neighbourhood of the carbonyl group of the acid component, in the presence of an amidase, protease, esterase or lipase as catalyst. Also claimed are (1) the production of optically active amino acid esters by: (a) enantioselectively acylating a racemic amino acid ester with a carboxylic acid ester, which carries a halo, N, O or S atom in the neighbourhood of the carbonyl group of the acid component, in the presence of an amidase, protease, esterase or lipase as catalyst; (b) separating the mixture obtained into optically active amino acid ester and optically active N-acyl-amino acid ester; and optionally (c) converting the optically active N-acyl-amino acid ester into the opposite amino acid ester enantiomer by amide cleavage; and (2) optically active amino acid esters of formula (I) and optically active N-acyl-amino acid esters of formula (II ) in which the NH2 and COOCH3 (or amino and COOR5 groups) are cis or trans to one another: R1 = 1-10C alkyl; 1-4C alkoxy; OH; NH2; halo; or Ar; R2 = H or 1-10C alkyl; X = halo; OR3; SR3; or NR3R4; R3 and R4 = H; 1-10C alkyl; or Ar; R5 = 1-10C alkyl or Ar; Ar = aryl optionally substituted by NH2, OH, 1-4C alkyl, 1-4C alkoxy or halo; i = 0-4; m = 0-2; n = 1-3.