Isolation of dihydroclavaminic acid, an intermediate in the biosynthesis of clavulanic acid

✍ Scribed by Jack E. Baldwin; Robert M. Adlington; Justin S. Bryans; Alain O. Bringhen; Janice B. Coates; Nicholas P. Crouch; Matthew D. Lloyd; Christopher J. Schofield; Stephen W. Elson; Keith H. Baggaley; Robert Cassels; Neville Nicholson

• Publisher: Elsevier Science
• Year: 1991
• Tongue: French
• Weight: 792 KB
• Volume: 47
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)86446-2

✦ Synopsis

A primary isotope effect was utilised in an in vitro study to allow the isolation and characterisation of an intermed& between proclavaminic acid and clavaminic acid, in clavulanic acid biosynthesis.1 Clavulanic acid (l), a medicinally important bicyclic ~lactam produced by Srreptomyces ckzvuligerus, is a potent inhibitor of ~lactamases from both Cram-positive and Cram-negative organisms and also possesses weak antibacterial activity. In vivo studies involving the feeding of labelled precursors have established that the carbons of the beta-lactam ring are derived from glycerol2 and those of the C-5 unit from ~ornithine2.

Subsequent in virro studies have demonstrated that the biosynthesis of clavulamc acid (1) proceeds via clavaminic acid (3) (Scheme I), which in turn is generated from proclavaminic acid (2a).43