CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry , 345 Lingling Road, Shanghai 200032, China.
J Org Chem. 2014 Jan 3;79(1):240-50. doi: 10.1021/jo402419h. Epub 2013 Dec 10.
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.
石杉碱 A、石杉碱 B 和石杉碱 U 是从小叶石杉（=石松）中分离得到的同系物，含量极微。高效地实现了石杉碱 A 的首次不对称全合成、石杉碱 B 的首次全合成和石杉碱 U 的首次全合成，总收率分别为 17%、10%和 9%，均从（R）-胡薄荷酮经 10-13 步反应得到。特征步骤包括钯催化的 Buchwald-Hartwig 偶联和 Heck 环化反应以及铱催化的烯烃异构化反应。这项工作确定了石杉碱 B 和石杉碱 U 的绝对构型，并揭示了天然石杉碱 A、石杉碱 B 和石杉碱 U 具有相同的绝对立体化学，从而为石杉碱 B 和石杉碱 U 在石杉碱 A 的生物合成中的潜在作用提供了支持。
