Enantioselective total synthesis of the potent antitumor agent (-)-mucocin using a temporary silicon-tethered ring-closing metathesis cross-coupling reaction

The enantioselective total synthesis of the annonaceous acetogenin (?)-mucocin (1) was accomplished using a triply convergent 12-step sequence (longest linear sequence) in 13.6% overall yield. This represents the first application of the temporary silicon-tethered (TST) ring-closing metathesis (RCM) cross-coupling reaction and the enantioselective alkyne/aldehyde addition to the synthesis of a complex annonaceous acetogenin. Moreover, all three fragments required for the coupling reactions are conveniently prepared in 5?6 steps from two readily available enantiomerically enriched epoxides. Finally, this synthesis stimulated the development of a new approach for the construction of 3-hydroxy-2,6-disubstituted tetrahydropyrans, using the bismuth tribromide-mediated reductive etherification reaction, which represents a motif that is prevalent in a wide range of pharmacologically significant natural products. Copyright © 2003 American Chemical Society.