New strategic intermediate for β-lactam antibiotic synthesis: Allenecarboxylates

Intra- and inter-molecular Michael addition of allenecarboxylates, derived from penicillins, may offer straightforward synthetic routes to 2-exo-methylenepenams and C(3)-substituted Δ³-cephems. Thus obtained 2-exo-methylenepenams are divergent intermediates for penem and penam families of antibiotics or potent β-lactamase inhibitors. The intermolecular Michael addition of the allenecarboxylates can achieve construction of the cephem framework as well as introduction of various C(3)-substituents, e.g., amino, sulfenyl, chloro, and alkenyl groups. In place of the allenecarboxylates, 3,4-disubstituted 2-[4-(phenylsulfonylthio)-2-oxoazetidin-1-yl]-2-butenoates work as a promising precursor of both the 2-exo-methylenepenams and 3-chloro-Δ³-cephems.