Enantioselective synthesis of an ophiobolin sesterterpene via a programmed radical cascade

Abstract

A radical route to ophiobolin rings Chemical ring-closing cascades resemble molecular yoga. One reactive site on a linear precursor can pull the whole molecule into a remarkably complex polycyclic arrangement. Cyclase enzymes rely on substantial internal scaffolding to guide this process during the biosynthesis of the ophiobolin sesterterpene frameworks, which comprise two pentagons sharing edges with an octagon. Brill et al. now show that the same motif is accessible abiotically by tweaking the cascade mechanism to rely on neutral radical intermediates in place of the positively charged activated sites in the biosynthetic pathways. Science , this issue p. 1078