State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, PR China.
J Org Chem. 2012 Sep 21;77(18):8174-81. doi: 10.1021/jo301545y. Epub 2012 Sep 10.
(+)-Alopecuridine, (+)-sieboldine A, and (-)-lycojapodine A, three structurally unique and related lycopodium alkaloids, have been synthesized in enantiomeric forms through an efficient strategy. The main synthetic approach for (+)-alopecuridine features a semipinacol rearrangement of hydroxyl epoxide to construct the spiro 6,9-azacarbocycles with an all-carbon quaternary center and a late-stage SmI(2)-mediated intramolecular coupling to form the 5-membered ring. Subsequently, the biomimetic synthesis of (+)-sieboldine A and (-)-lycojapodine A was accomplished successfully through two different bioinspired oxidations after a wide search for the oxidation methods. As a result, (+)-sieboldine A was derived from (+)-alopecuridine through an N-oxidation/nitrone formation process and (-)-lycojapodine A through an interesting cyclic hemiketal formation/oxidative diol cleavage pathway. These results confirmed the biogenetic relationship among the three alkaloids.
（+）-白毛藤碱、（+）-延胡索乙素 A 和（-）-藜芦定 A 是三种结构独特且相关的石松生物碱，通过一种有效的策略以对映异构体的形式被合成。（+）-白毛藤碱的主要合成方法是羟基环氧化物的半频哪醇重排，构建具有全碳季碳原子的螺 6,9-氮杂碳环，并在后期通过 SmI(2)介导的分子内偶联形成 5 元环。随后，通过广泛寻找氧化方法，成功地通过两种不同的仿生氧化反应完成了（+）-延胡索乙素 A 和（-）-藜芦定 A 的仿生合成。结果，（+）-延胡索乙素 A 是通过（+）-白毛藤碱的 N-氧化/氮酮形成过程得到的，（-）-藜芦定 A 是通过有趣的环状半缩醛形成/氧化二醇裂解途径得到的。这些结果证实了这三种生物碱之间的生物发生关系。
