ENZYMATIC HYDROLISIS OF CEPHALOSPORINS DERIVING FROM THE CHEMICAL BROADENING OF THE CILLIN G RING AND ENZYMATIC SYNTHESIS OF SEMISYNTHETIC CEPHALOSPORINS

摘要

1480850 Enzymatic hydrolysis on synthesis of cephalosporins SNAMPROGETTI SpA 16 Dec 1974 [20 Dec 1973] 54336/74 Heading C2C Hydrolysis of a cephalosporin produced by increasing the size of the thia ring of penicillin G and/or the synthesis of a semi-synthetic cephalosporin from a 7-aminocephalosporanic acid whose thia ring has been produced by increasing the size of the thia ring of penicillin G, is effected by contacting the said cephalosporin or 7-aminocephalosporanic acid in a phosphate buffer at a pH at which said hydrolysis or synthesis takes place with bacterial cells of a strain of Escherichia coli or with penicillin acylase extracted from said cells and purified, a said synthesis being carried out in the presence of a molar excess of an acylating agent. Preferably cephalosporin G is hydrolysed to yield 7 - aminodesacetoxycephalosporanic acid. Alternatively a synthesis comprising reacting 7 - aminodesacetoxycephalosporanic acid or (7 - ADCA) 7 - aminocephalosporanic acid (7 - ACA) with a compound of the formula in which X1 is H or a group inert during said synthesis, X11 is an alkoxy or -NH 2 group and X111 is H or a -NH 2 group, may be effected in the presence of the cells or enzyme and phosphate buffer. For example, 7-ADCA may be reacted with D(-)phenyl glycine methyl ester HCl(PGM) to obtain cephalexin, 7-ACA may be reacted with PGM to obtain cephaloglycine, or 7-ACA may be reacted with phydroxyphenylglycine ethyl ester to form 7#[21 - amino - 2 - (4 - hydroxyphenyl)acetamido] - 3 - hydroxymethyl(acetate)ceph- 3-em-4-carboxylic acid.