Club mosses Huperzia serrata

Huperzine A (1), isolated from the club moss Huperzia serrata (syn. Lycopodium serratum), has been used in the treatment of Alzheimer s disease (AD). The club moss... 

Huperzia serrata (moss), Lycopodium selago (fir club moss) — not to be confused with non-toxic L. clanatum... 

Acetate is also a precursor of several groups of alkaloids in the form of a polyketide chain that interacts with an unknown nitrogen source (as in the terpene alkaloids). Examples of acetate-derived alkaloids are coniine—the toxic principle of Conium maculatum, pinidine—from several Pinus species, and the naphthy-lisoquinoline alkaloids (e.g., ancistrocladine)—showing antimalarial and anti-HIV activity. The latter alkaloids are apparently derived from the oxidative coupling of two pentaketide units. Huperzine A, currently in clinical trials for the treatment of Alzheimer s disease and isolated from the club moss (Serrata huperzia), is derived from a polyacetate precursor (Fig. 46). 

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]. 

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