title: Synthesis of (±)-7-hydroxylycopodine.
abstract: A seven-step synthesis of (±)-7-hydroxylycopodine that proceeds in 5% overall yield has been achieved. The key step is a Prins reaction in 60% sulfuric acid that gave the key tricyclic intermediate with complete control of the ring fusion stereochemistry. A one-pot procedure orthogonally protected the primary alcohol as an acetate and the tertiary alcohol as a methylthiomethyl ether. The resulting product was converted to 7-hydroxydehydrolycopodine by heating with KO-t-Bu and benzophenone in benzene followed by acidic workup. During unsuccessful attempts to make optically pure starting material, we observed the selective Pt-catalyzed hydrogenation of the 5-phenyl group of a 4,5-diphenyloxazolidine under acidic conditions and the Pt-catalyzed isomerization of the oxazolidine to an amide under neutral conditions. In attempts to hydroxylate the starting material so that we could adapt this synthesis to the preparation of (±)-7,8-dihydroxylycopodine (sauroine) we observed the novel oxidation of a bicyclic vinylogous amide to a keto pyridine with Mn(OAc)(3) and to an amino phenol with KHMDS and oxygen.
authors.affiliation: Department of Chemistry MS 015, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Lin
authors.forename: Robert
authors.initials: R
authors.lastname: Causey
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Garcia
authors.forename: Barry B
authors.initials: BB
authors.lastname: Snider
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011807:Quinolizines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C557931:7-hydroxylycopodine; D000470:Alkaloids; D011807:Quinolizines