Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin

The halogenated 6-spiroepoxypenicillins are a series of novel semisyntheticβ-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3R-compounds possess notable Gram-positive antibacterial activity and potentβ-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retainβ-lactamase inhibitory activity.