CEPHALOSPORIN BIOSYNTHESIS - A BRANCHED PATHWAY SENSITIVE TO AN ISOTOPE EFFECT

Journal article

Incubation of penicillin N (3a) with partially purified deacetoxy/deacetylcephalosporin C synthase (DAOC/DAC synthase) from Cephalosporium acremonium CO 728 gave in addition to the expected products, deacetoxycephalosporin C and deacetylcephalosporin C, a third β-lactam metabolite as a 3β-hydroxy-3α-methylcepham (9a). Production of the 3β-hydroxycepham was promoted from [3-2H]penicillin N (3b) which was rationalised by the operation of a kinetic isotope effect on a branched pathway in the enzymic process. The oxygen of the 3β-hydroxy group was shown to be derived in part from molecular oxygen. In addition, the 2β-methyl group of penicillin N was shown to be incorporated into C2 of the 3β-hydroxy-3α-methylcepham, a result in stereochemical accord with the equivalent transformation of the 2β-methyl group of penicillin N into C2 of deacetoxycephalosporin C1. A mechanistic interpretation, consistent with these observations, is offered. © 1991.

Authors: Baldwin, J; Adlington, R; Crouch, N; Schofield, C; Turner, N

• Publication status: Published
• Journal: TETRAHEDRON
• Volume: 47
• Issue: 47
• Pages: 9881-9900
• Publication date: 1991-12-02
• DOI: 10.1016/S0040-4020(01)80725-0
• ISSN: 0040-4020