title: The first total synthesis of (+/-)-ingenol.
abstract: The first total synthesis of (+/-)-ingenol has been achieved. The key features of the synthesis include the use of a highly diastereoselective Michael reaction to fix the C-11 methyl stereochemistry and the incorporation of the dimethylcyclopropane via diastereoselective carbene addition to the Delta13,14 olefin. The intramolecular dioxenone photoaddition-fragmentation sequence leads to the establishment of the critical C-8/C-10 trans intrabridgehead stereochemistry, a central challenge in the synthesis of ingenanes. The completion of the synthesis proceeds using the C-6alpha hydroxymethyl group as the sole handle for oxidation of seven contiguous carbon centers.
authors.affiliation: Department of Chemistry, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. winkler@sas.upenn.edu
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Winkler
authors.forename: Meagan B
authors.initials: MB
authors.lastname: Rouse
authors.forename: Michael F
authors.initials: MF
authors.lastname: Greaney
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Harrison
authors.forename: Yoon T
authors.initials: YT
authors.lastname: Jeon
mesh_terms: D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
chemical_list: D004224:Diterpenes; C008125:ingenol