Lycopodium alkaloids synthetic approach

While only a snapshot of the proposed biosynthetic picture for complanadine A has been presented above, we considered an alternative approach in our synthetic strategy analysis (as shown below in Fig. 11.3) that also put into focus the close connections between complanadine A, which would arise from a dimerization of the (S-obscurine precursor 21, and the Lycopodium alkaloids lycoposerramine R (23) and fastigiatine (25). The details of this strategic approach are the subject of this chapter. 

Isomunchnones play a large part in the synthetic efforts Padwa and co-workers (91-94,96,98,110,111). The Lycopodium alkaloids are a large family of natural products and have inspired numerous synthetic routes to approach these compounds. Interest in this class of alkaloids stems from the myriad of biological properties they exhibit. Padwa utilized the carbonyl ylide methodology in tandem with a cationic 71-cyclization to complete a formal synthesis of ( ) lycopodine (Scheme 4.55) (96,112). 

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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