title: Divergent total synthesis of the Lycopodium alkaloids huperzine A, huperzine B, and huperzine U.
abstract: Huperzine A, huperzine B, and huperzine U are congeners isolated from the Chinese herb Huperzia serrata (= Lycopodium serratum ) in minuscule amounts. The most efficient total synthesis of huperzine A, the first asymmetric total syntheses of huperzine B, and the first total synthesis of huperzine U have been achieved efficiently in overall yields of 17%, 10%, and 9%, respectively, each spanning 10-13 steps from (R)-pulegone. The featured steps include palladium-catalyzed Buchwald-Hartwig coupling and Heck cyclization reactions and an Ir-catalyzed olefin isomerization reaction. This work has established the absolute configurations of huperzine B and huperzine U and revealed that natural huperzine A, huperzine B, and huperzine U possess the same set of absolute stereochemistries, thus providing support for the potential role of huperzine B and huperzine U in the biosynthesis of huperzine A.
authors.affiliation: CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry , 345 Lingling Road, Shanghai 200032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Fu
authors.forename: Guang-Qiang
authors.initials: GQ
authors.lastname: Xu
authors.forename: Bing-Feng
authors.initials: BF
authors.lastname: Sun
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Lin
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000081005:Cyclohexane Monoterpenes; D004365:Drugs, Chinese Herbal / Q000138:chemical synthesis* / Q000737:chemistry; D032502:Lycopodium / Q000737:chemistry*; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D000081005:Cyclohexane Monoterpenes; D004365:Drugs, Chinese Herbal; D039821:Monoterpenes; D012717:Sesquiterpenes; C000590896:huperzine U; C050426:huperzine A; C053016:huperzine B; C039648:pulegone