Alkaloids lycopodium

Lysine-Derived Alkaloids. Just as putresciae (36) derived from ornithine (23) is coasidered the pregenitor of the aucleus fouad ia pyrrolidine-containing alkaloids, so cadavetiae [462-94-2] (44), C H 4N2, derived from lysiae (24) is the idealized pregenitor of the 1-dehydropiperidine [28299-36-7] nucleus (45), C H N, found in the pomegranate, Sedum Dobelia, Dupin, and Lycopodium alkaloids (39). 

The stereoselective addition of allylsilanes to enones was used to control the relative C-3-C-5 configuration in total syntheses of lycopodium alkaloids and of fawcettimine29,30. 

Lycopodium alkaloids Lycopodiaceae sp. SiOj CHClj-MeOH-NHj Dragendorff s reagent Identification 9... 

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... 

Zard and coworkers [32] reported a simple approach to create another group of natural products, namely the lycopodium alkaloids [15]. These authors first investigated the reaction of O-benzoyl-N-allylhydroxylamide 3-60 with tributyltin hydride and ACCN in refluxing toluene, which led (after formation of the N-radical 3-61 in a 5-exo-trig/5-exo-trig cyclization) to the undesired pyrrolidine 3-62 in 48% yield. Nevertheless, a small structural modification, namely the placement of a chlorine atom at the allyl moiety as in 3-63, induced a 5-exo-/G-endo- instead of the 5-exo-/5-... 

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

Chart 6.1 Representative Lycopodium alkaloids from each structural class... 

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]. 

Representative examples of recent Lycopodium alkaloid total syntheses (2009-current) ... 

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... 

Fig. 11.3 Potential synthetic link of selected Lycopodium alkaloids to obscurines...

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. 

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. 

Nyembo et al. [15] proposed in 1978 that the amino acid 34 and other compounds of general structure 35> known as phlegmarines, the stereochemistry of which is not specified, may be intermediates involved in the biosynthesis of Lycopodium alkaloids. 

A structure proposed for the lycopodium alkaloid, annotinine, was a derivative of 7-azabicyclo[2.2.1]heptane, but this is incorrect, and no naturally occurring compound is known to contain this ring system. On the other hand, the 7-oxabicyclo[2.2.1]heptane ring system is present... 

Gao, W Li, Y Jiang, S. and Zhu, D. 2000. Three lycopodium alkaloid A-oxides from Huperzia serrata. Planta Medica, 66 664-667. 

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