Lycopodium alkaloids synthesis

Another effective combination of two radical cyclization steps has been demonstrated by Sha and coworkers during the course of the first total synthesis of (+)-paniculatine (3-24), a natural alkaloid belonging to the subclass of Lycopodium alkaloids [13]. 3-24 has a unique tetracyclic scaffold with seven stereogenic centers [14]. Although no special features of (+)-paniculatine have so far been documented, other Lycopodium alkaloids are reported to be potent acetylcholinesterase inhibitors, or show promising results in the treatment of Alzheimer s disease [15]. When... 

Scheme 3.17. Synthesis of pyrrolidines and indolizidines as well as of the lycopodium alkaloid 13-desoxyserratine (3-65).

Based on their unique structures and complicated ring skeletons, the Lycopodium alkaloids have attracted sustained attention from the synthetic community [2e, 17]. Our synthesis of serratezomine A (1) [18] currently stands alone, but the structural similarity between serratezomine A and serratinine (4) compels a discussion of prior work towards the latter. This includes syntheses of the framework [19] of serratinine (4) or similar molecules and one total synthesis [20]. 

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. 

The elegant procedure of Schumann to prepare 38 required two compounds, aminoketal 42 (Scheme 11.6a) and dihydropyridone 45 (Scheme 11.6b). As with many syntheses of Lycopodium alkaloids, the synthesis of aminoketal 42 began with... 

Similarly, we anticipate that boronic ester 52 should prove highly useful for the synthesis of other lycodine-derived Lycopodium alkaloid pseudodimers including complanadines D and E (see Scheme 11.2) as well as unnatural analogues for biological studies. This is the direction of our ongoing research in this area. 

A third total synthesis of luciduline in its racemic form was reported by Szychowski and MacLean in 1979 [14]. The final aim of the authors was to synthesise an intermediate which may be involved in the biosynthesis not only of luciduline itself but also of other members of the Lycopodium alkaloids family. 

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). 

Heathcock has extended his elegant approach to the synthesis of the Lycopodium alkaloids, reviewed last year (c/. Vol. 10, p. 207) in the case of lycopodine (15),7 to provide the first total synthesis of lycodine (7).8 The synthesis (Scheme 1) proceeds from the previously described cyano-enone (16) in just... 

Concise and efficient total synthesis of Lycopodium alkaloid magellanine. Angewandte Chemie, International Edition, 41 (21), 4090 1093. 

Comins, D.L. and Williams, A.L. (2001) Model studies toward the total synthesis of the lycopodium alkaloid spirolucidine. 

Decahydroquinoline Alkaloids.—A review on the total synthesis of lycopodium alkaloids has appeared it includes syntheses of luciduline.25 Additional total syntheses of ( )-gephyrotoxin26 and ( )-perhydrogephyrotoxin27 have been described, and ( )-depentylperhydrogephyrotoxin has been synthesized via an interesting cyclization of a vinylogous TV-acyliminium ion.28... 

This reaction was used in a synthesis of the lycopodium alkaloid 8-deoxyser-ratinine (A). ... 

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