A Strategy for the Convergent and Stereoselective Assembly of Polycyclic Molecules

The stereoselective
oxidative coupling of cyclic ketones via silyl
bis-enol ethers followed by ring-closing metathesis is shown to be
a general and powerful reaction sequence for the preparation of diverse
polycyclic scaffolds from simple precursors. The modular strategy
successfully constructs substructures prevalent in numerous bioactive
natural product families, varying in substitution and carbocyclic
composition. Several of the prepared compounds were shown to possess
potent cytotoxic activity against a panel of tumor cell lines. The
utility of this strategy was further demonstrated by a concise and
highly convergent 17-step formal synthesis of the complex antimalarial
marine diterpene, (+)-7,20-diisocyanoadociane.