Huperzia Lycopodium alkaloids

Gao, W Li, Y Jiang, S. and Zhu, D. 2000. Three lycopodium alkaloid A-oxides from Huperzia serrata. Planta Medica, 66 664-667. 

Gao W, Li Y, Jiang S, Zhu D. Three lycopodium alkaloid N-oxides from Huperzia serrata. Planta Med 2000 66 664-7. 

Tan C-H, Wang B-D, Jiang S-H, Zhu D-Y. New lycopodium alkaloids from Huperzia serrata. Planta Med 2002 68 186-8. 

The club mosses are the only natural sources of lycopodium alkaloids and they are vulnerable slow-growing plants which are very difficult to cultivate in addition, their alkaloid content is low, e.g., about 0.005-0.025 %inH. serrata for the much demanded hupA [17]. At present, the market is supplied with H. serrata plant material and isolated hupA primarily from the wild growing plants of H. serrata and other Huperzia species in China, which are subsequently becoming endangered species [3, 8]. Accordingly, it is important to find sustainable methods to produce these compounds. The synthesis of hupA has been studied since 1989 and different approaches have been reported in the literature but none of them seem to be industrially feasible [17]. However, a new eight-step enantioselective synthetic route to hupA in 35 5 % yield was recently published by Tun et al., and the authors conclude that the method will provide a reliable supply of this compotmd for future applications [33]. 

This review describes the recent studies on Lycopodium alkaloids isolated from the genus Lycopodium and Huperzia, the proposed biogenetic pathway, and the syntheses of Lycopodium alkaloids based on these biogenetic proposals. In section II, all of the Lycopodium alkaloids isolated so far, and including our recent work, are surveyed, while sections III and IV mainly deal with the biogenetic pathways and the total syntheses of the Lycopodium alkaloids, respectively. In sections V, VI, and VII, pharmacology, total synthesis, and SAR studies, respectively of huperzine A (I) are briefly surveyed. 

Huperzine A, a potent anticholinesterase alkaloid, and huperzine B were separated from a Chinese medicinal herb, Huperzia serrata (Thunb) Trev. Lycopodium serratum Thunb.), (Lycopodiaceae), by Liu et al [25]. The plant was used in Zhejiang Province of China for treatment of some mental disorders. 

Furthermore, ten new alkaloids, lycoposerramines F (30), G (31), H (32), I (33), J (34), K (35), L (36), M (37), N (38), and -O (39), having lycopodine-related structures, were isolated from the club moss Lycopodium serratum and their structures were elucidated on the basis of spectroscopic analysis and/or chemical transformation (34). Lycoposerramines F (30) and J (34) were the same structures as miyoshianines A and B, respectively, isolated from Huperzia miyoshiana (50). 

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