Γ-lactam Analogues Research Articles

γ-Lactam analogues of carbapenems

γ-Lactam analogues of carbapenems have been synthesized using a [3+2] cyclization approach. Slight antibiotic activity was observed in one case.

γ-Lactam analogues of carbapenicillanic acids

The syntheses and biological activities of the γ-lactam analogues ( endo -25), ( exo -25) and (26) of carbapenicillanic acids are described. The strategy employed for the synthesis of 26 effected construction of a γ-lactam onto a preformed azetidine, followed by direct amination of the lactam enolate (20) with diphenylphosphinoyl-hydroxylamine. X-ray crystallographic studies demonstrated that the analogues bore a strong morphological resemblance to carbapenicillanic acids; however, they were shown to be devoid of antibacterial and beta-lactamase inhibitory activity. 1

γ-Lactam analogues of penicillanic and carbapenicillanic acids

Abstract Synthesis and biological activity of γ-lactam analogues of penicillanic and carboapenicillanic acids, and the sodium periodate mediated rearrangement of pyrrolidine-2,3-diones are described. 1,3- Dipolar addition of cyclic nitrone (6) and methyl acrylate afforded the bicyclic adducts (7a) and (7b). Reductive cleavage of the N-O bond and subsequent cyclisation of a regioisomer (11a) gave the γ-lactams (12a) and (12b) in a ratio of 85 : 15. They are transformed to the carbapenam analogues (1)-(4). Their stereochemistry was assigned according to the X-ray structure of the γ-lactam (12b). Benzyl 6-oxopenicillanate (20) was directly transformed to the γ-lactam analogue (5) via a novel ring expansion. These synthetic analogues did not show antibiotic activity or β-lactamase inhibition. Treatment of pyrro1idine-2,3-diones (25a) and (25b) with sodium periodate gave ring contracted β-lactams (26a) and (26b) respectively. Similar treatment of (27) followed by diazomethane afforded an unexpected spiro epoxide.