title: Total syntheses of bryostatins: synthesis of two ring-expanded bryostatin analogues and the development of a new-generation strategy to access the C7-C27 fragment.
abstract: Herein, we report the synthesis of novel ring-expanded bryostatin analogues. By carefully modifying the substrate, a selective and high-yielding Ru-catalyzed tandem enyne coupling/Michael addition was employed to construct the northern fragment. Ring-closing metathesis was utilized to form the 31-membered ring macrocycle of the analogue. These ring-expanded bryostatin analogues possess anticancer activity against several cancer cell lines. Given the difficulty in forming the C16-C17 olefin at a late stage, we also describe our development of a new-generation strategy to access the C7-C27 fragment, containing both the ring B and C subunits.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305, USA. bmtrost@stanford.edu
authors.forename: Barry M
authors.initials: BM
authors.lastname: Trost
authors.forename: Hanbiao
authors.initials: H
authors.lastname: Yang
authors.forename: Guangbin
authors.initials: G
authors.lastname: Dong
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D054713:Bryostatins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D003500:Cyclization; D003516:Cycloparaffins / Q000737:chemistry*; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D003516:Cycloparaffins; D018942:Macrolides; D010165:Palladium; D012428:Ruthenium