Total Synthesis of the Lycopodium Alkaloid Complanadine

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. 

As a whole, the Lycopodium alkaloids consist of over 270 members, and the number of natural products in this family continues to grow [1], The natural products are divided into four structural classes, three of which are represented by the parent 

From a laboratory synthesis standpoint, it was difficult to envision a synthesis of complanadine A along the proposed biosynthetic lines, given the propensity with which compounds such as 15a and 15b undergo disproportionation or oxidation to afford 2 and 14 as recognized in the work of Schumann and coworkers [10]. 

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. 

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