title: Thionium ion initiated medium-sized ring formation: the total synthesis of asteriscunolide D.
abstract: The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a γ-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
authors.forename: Barry M
authors.initials: BM
authors.lastname: Trost
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Burns
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bartlett
authors.forename: Thomas
authors.initials: T
authors.lastname: Tautz
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Weiss
mesh_terms: D019659:Asteraceae / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D007477:Ions / Q000138:chemical synthesis / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D007477:Ions; D007783:Lactones; D000644:Quaternary Ammonium Compounds; D012717:Sesquiterpenes; C449600:asteriscunolide D; C059915:thionium