title: Palladium-catalyzed asymmetric allylic substitution of 2-arylcyclohexenol derivatives: asymmetric total syntheses of (+)-crinamine, (-)-haemanthidine, and (+)-pretazettine.
abstract: Much interest has been shown in Amaryllidaceae alkaloids as synthetic targets due to their wide range of biological activities. Over 100 alkaloids have been isolated from members of the Amaryllidaceae family; most of them can be classified into eight skeletally homogeneous groups. We have succeeded in the first asymmetric total syntheses of the crinane-type alkaloids (+)-crinamine (1), (-)-haemanthidine (2), and (+)-pretazettine (3). The starting cyclohexenylamine 14 was obtained from allyl phosphonate 11c by palladium-catalyzed asymmetric amination in 82% yield and with 74% ee. The product was recrystallized from MeOH. Interestingly, (-)-14 with 99% ee was obtained from the mother liquor (74% recovery). Intramolecular carbonyl-ene reaction of (-)-10 proceeds in a highly stereoselective manner to give hexahydroindole derivative 9 as the sole product. In the Lewis-acid-catalyzed carbonyl-ene reaction, an interesting rearrangement product, 20, was isolated in high yield. From 9, (+)-crinamine was synthesized. Thus, the asymmetric total synthesis of (+)-crinamine was achieved in 10 steps from 11c, and the overall yield is 19%. The total synthesis of (-)-haemanthidine was also achieved from 9 by a short sequence of steps.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Toyoki
authors.initials: T
authors.lastname: Nishimata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sato
authors.forename: Miwako
authors.initials: M
authors.lastname: Mori
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis*; D000498:Allyl Compounds / Q000737:chemistry*; D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D002384:Catalysis; D003510:Cyclohexanes / Q000737:chemistry*; D053138:Cyclohexenes; D026121:Indole Alkaloids / Q000138:chemical synthesis*; D007212:Indolizines / Q000138:chemical synthesis*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D010617:Phenanthridines / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D000498:Allyl Compounds; D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D003510:Cyclohexanes; D053138:Cyclohexenes; D026121:Indole Alkaloids; D007212:Indolizines; D010617:Phenanthridines; C052568:cyclohexene; C010766:pretazettine; C083906:hemanthidine; D010165:Palladium; C411129:crinamine