Process for the preparation of beta-lactam compounds

1. A process for the synthesis of a semi-synthetic β-lactam compound from a nucleus and a side chain selected from the group consisting of D-phenylglycine and D-dihydro-phenylglycine in the form of a side chain ester and an enzyme catalyzing the coupling of the side chain ester to the nucleus comprising the steps of

(a) converting a free side chain selected from the group consisting of D-phenylglycine and D-dihydro-phenylglycine with an alcohol to form a mixture comprising the corresponding side chain ester;

(b) forming the semi-synthetic β-lactam compound by mixing the mixture obtained in step (a) with a nucleus and the enzyme to form the semi-synthetic β-lactam compound,

with the proviso that the side chain ester formed in step (a) is not isolated as a solid intermediate.

2. Process according to claim 1 wherein the mixture obtained in step (a) is purified before forming the semi-synthetic β-lactam compound in step (b).

3. Process according to claim 1 wherein the nucleus is selected from the group consisting of 6-aminopenicillanic acid (6-APA), 7-amino-deacetoxy-cephalosporanic acid (7-ADCA), 7-aminocephalosporanic acid (7-ACA) and 7-amino-3-chloro-3-cephem-4-carboxylate (7-ACCA).

4. Process according to claim 1 wherein the semi-synthetic β-lactam compound is selected from the group consisting of Ampicillin, Cephalexin, Cephradine and Cefaclor.

5. Process according to claim 1 wherein the alcohol is methanol or ethanol.

6. Process according to claim 5 wherein the alcohol is methanol.

7. Process according to claim 1 wherein the enzyme is a penicillin G acylase.

8. Process according to claim 7 wherein the penicillin G acylase is from Escherichia coli.

9. Process according to claim 7 wherein the enzyme is in an immobilized form.