title: Eremophilane sesquiterpenes from capsidiol.
abstract: A series of eremophilane sesquiterpene alcohols and hydrocarbons was prepared from the phytoalexin capsidiol (1) for mechanistic studies with epiaristolochene synthase and epiaristolochene dihydroxylase. Among them, 3-deoxycapsidiol (10) was obtained through selective derivatization and reductive cleavage of the equatorial 3 alpha hydroxyl group. Two novel isomers of aristolochene and eremophilene were accessed from the 1- and 3-deoxycapsidiol isomers. 4-Epieremophilene (17) was obtained by conjugate reduction of epiaristolochen-1-one tosylhydrazone with catecholborane followed by sulfinate elimination and diimide rearrangement. Epimerization of epiaristolochen-3-one (27a) at the C4 methyl followed by reductions led to the previously unknown aristolochene isomer, eremophila-9(10),11(12)-diene (30). Optical rotations and characteristic (1)H NMR data for the related eremophilenols and dienes are collected in Tables 1 and 2. Finally, bioassays were used to assess the antifungal potencies of capsidiol and its synthetic derivatives. The minimum inhibitory concentration for capsidiol (3-10 ng) was at least 1 order of magnitude lower than that of any of the derivatives and considerably lower than those previously reported for ketoconazole, nystatin, and propiconazole.
authors.affiliation: Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhao
authors.forename: David J
authors.initials: DJ
authors.lastname: Schenk
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.forename: Joe
authors.initials: J
authors.lastname: Chappell
authors.forename: Robert M
authors.initials: RM
authors.lastname: Coates
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010946:Plants, Medicinal / Q000737:chemistry; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C018286:eremophilane compounds; C081843:capsidiol