Lycopodium alkaloids complanadine A

As is evident from its structure, complanadine A is comprised of two molecules of the natural product lycodine (2), which are joined at the 2 and 3 positions of the two monomers, respectively (see 1 for numbering). Although there are other examples of dimeric Lycopodium alkaloids, the pseudosymmetric variants are not very common. Therefore, a synthesis of complanadine A could offer opportunities to study the properties and intricacies of the reactivity of the pseudodimeric Lycopodium alkaloids. 

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. 

Ishiuchi K, Kubota T, Ishiyama H, Hayashi S, Shibata T, Mori K, et al. Lyconadins D and E, a complanadine E, new Lycopodium alkaloids from Lycopodium complana-tum. Bioorg Med Chem 2011 19(2) 749-53. 

Complanadine (155), a member of the family of lycopodium alkaloids, has more recently been identified as an inducer of neurotropic factor excretion. The synthesis of this almost symmetrical alkaloid, potentially interesting for the treatment of diseases of the central nervous system, was based on two late-stage crossed [2 + 2 + 2] pyridine formation reactions that delivered the central bipyridyl unit. 

Complanadine A (43) is the first dimeric alkaloid containing a lycodine-type C16N2 skeleton among the many Lycopodium alkaloids reported so far. 

Morita H, Ishiuchi K, Haganuma A, Hoshino T, Obara Y, Nakahata N, Kobayashi J (2005) Complanadine B, obscurumines A and B, new alkaloids from two species of Lycopodium. Tetrahedron 61 1955-1960... 

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