Directed hydrogenation of acyclic homoallylic alcohols: enantioselective syntheses of (+)- and (-)-laurenditerpenol.

Laurenditerpenol is the first marine natural product shown to inhibit hypoxia-inducible factor 1 (HIF-1) activation. Preclinical studies support that the inhibition of HIF-1 is one of the molecular targets for antitumor drug discovery. The synthetically challenging molecular architecture of laurenditerpenol, its absolute stereostructure, and the biological activity of several diastereoisomers were accomplished by our group in 2007 by diastereoselective synthesis. Herein, we report enantioselective syntheses of both enantiomers of laurenditerpenol involving sequential Michael addition and remote homoallylic hydroxyl group-directed asymmetric hydrogenation at ambient temperature and pressure as key reaction steps. The current approach is elegant and overall more efficient than the ones previously reported in the literature.