N-Heterocyclic Carbene Catalyzed Oxidative Macrolactonization: Total Synthesis of (+)-Dactylolide

摘要

(+)-Dactylolide (1, Figure 1) is a cytotoxic 20-membered macrolide isolated from the Vanuatu sponge Dactylospongia sp by Riccio and co-workers. It possesses unique structural features which include a 2,6-cis-2-(4-oxo-2-butenyl)tetra-hydropyran, a highly unsaturated 20-membered macrolac- tone, and an α-chiral aldehyde. (+)-Dactylolide (1) displayed modest tumor cell growth inhibitory activities in leukemia and ovarian cancer cell lines and the mode of action has not been fully understood. Not surprisingly, as a result of the architectural complexity, biological profile, and enantiomeric relationship of the macrolactone core in 1 with natural (—)-zampanolide (2, Figure 1),1 and unnatural (—)-dacty-lolide have attracted considerable interest from a number of synthetic groups, thus culminating in the first total synthesis by Smith and co-workers.