Bispyrrole Antibiotics From The Deep

A veritable treasure trove of medicinally relevant compounds has once again been found by plumbing the oceans' depths. William Fenical and coworkers at University of California, San Diego's Scripps Institution of Oceanography have identified an unusual pair of structurally related antibiotics isolated from bacteria that inhabit ocean sediments (Org. Lett., DOI: 10.1021/ol702952n).

The compounds, dubbed marinopyrrole A and B, possess an N,C2-linked bispyrrole motif that's never been observed in natural products. Four ortho substituents flank the biaryl bond of the densely halogenated compounds, establishing an axis of chirality. Postdoctoral fellow Chambers C. Hughes isolated the molecules as single atropo-enantiomers, suggesting that their biosynthesis involves a critical enzyme-mediated pyrrole coupling.

Fenical and his team were able to isomerize marinopyrrole A to its nonnatural atropo-enantiomer by heating it. This enantiomer, along with the natural marinopyrroles, exhibits promising antimicrobial activity against methicillin-resistant Staphylococcus aureus.

By focusing a synthetic effort on the marinopyrroles' novel bispyrrole structure, Fenical says, medicinal chemists might discover new compounds for fighting drug-resistant infections.