title: Synthesis of the Cortistatin Pentacyclic Core by Alkoxide-Directed Metallacycle-Mediated Annulative Cross-Coupling.
abstract: 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.
authors.affiliation: Burke Laboratory, Department of Chemistry, Dartmouth College , Hanover, New Hampshire 03755, United States.|Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.forename: Claudio
authors.initials: C
authors.lastname: Aquino
authors.affiliation: Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Greszler
authors.affiliation: Burke Laboratory, Department of Chemistry, Dartmouth College , Hanover, New Hampshire 03755, United States.|Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Micalizio
mesh_terms: D000080:Acetals / Q000737:chemistry; D000478:Alkylation; D003500:Cyclization; D007189:Indans / Q000737:chemistry; D009479:Neuropeptides / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000080:Acetals; D007189:Indans; D009479:Neuropeptides; C099323:cortistatin; C531997:hydrindane