title: Total synthesis of bryostatin 1.
abstract: Bryostatin 1 is a marine natural product that is a very promising lead compound because of the potent biological activity it displays against a variety of human disease states. We describe herein the first total synthesis of this agent. The synthetic route adopted is a highly convergent one in which the preformed, heavily functionalized pyran rings A and C are united by "pyran annulation", the TMSOTf-promoted reaction between a hydroxyallylsilane appended to the A-ring fragment and an aldehyde contained in the C-ring fragment, with concomitant formation of the B ring. Further elaborations of the resulting very highly functionalized intermediate include macrolactonization and selective cleavage of just one of five ester linkages present.
authors.affiliation: Department of Chemistry, University of Utah, 315 South 1400 East, Room 2020, Salt Lake City, Utah 84112, United States. keck@chem.utah.edu
authors.forename: Gary E
authors.initials: GE
authors.lastname: Keck
authors.forename: Yam B
authors.initials: YB
authors.lastname: Poudel
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Cummins
authors.forename: Arnab
authors.initials: A
authors.lastname: Rudra
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Covel
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D054713:Bryostatins / Q000138:chemical synthesis* / Q000737:chemistry; D011714:Pyrans / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D054713:Bryostatins; D011714:Pyrans; C046785:bryostatin 1