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Synthesis of the Cortistatin Pentacyclic Core by Alkoxide-Directed Metallacycle-Mediated Annulative Cross-Coupling
- Aquino, Claudio, Greszler, Stephen N., Micalizio, Glenn C.
- Organic letters 2016 v.18 no.11 pp. 2624-2627
- alcohols, alkylation, chemical structure, chemoselectivity, cross-coupling reactions, regioselectivity, stereoselectivity
- The pentacyclic core skeleton of the cortistatins has been prepared in a stereoselective fashion by strategic use of an alkoxide-directed metallacycle-mediated annulative cross-coupling. This metal-centered tandem reaction delivers a polyunsaturated hydrindane and establishes the C13 stereodefined quaternary center with high levels of stereocontrol. Subsequent regio- and stereoselective global hydroboration results in the realization of the DE-trans ring fusion and a tertiary alcohol at C8. Establishment of the ABC-tricyclic subunit was then accomplished through phenolic oxidation/trans-acetalization, chemoselective reduction, regioselective cleavage, and intramolecular alkylation at C5.