Lycopodium alkaloids, examples

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. 

The saturated system, i.e. quinolizidine (4), is far more important due to the bewildering profusion of quinolizidine alkaloids in nature it has been estimated that 25-30% of all known alkaloids belong to the quinolizidine-indolizidine group. Some examples of alkaloids containing the quinolizidine structure are given below in structures (5)-(10) the simple quinolizidine alkaloids lupinine (5) and nupharidine (6) the Lycopodium alkaloid lycopodine (7) with a hydrojulolidine... 

Various approaches to the assembly of the 1,3-dienes that engage in the Diels-Alder cycloaddition reactions leading to substrates for DPM and ODPM processes have been reported. Thus, for example. Yen and Liao demonstrated, during the course of a total synthesis of the Lycopodium alkaloid magellanine, that oxidation of acetovanillone (109) rScheme 9.151 with diacetoxyiodobenzene (DAIB) in the presence of methanol afforded the o-benzoquinone monoketal 110. The latter conpound engaged in an in situ Diels-Alder reaction with added cyclopentadiene (111) and the resulting adduct 112 proved to be an excellent substrate for the ODPM rearrangement reaction. Thus, photolysis of 112 as a solution in acetone afforded the pivotal tetracyclic diketone 113 in 92% yield. 

Cope itself. For example, Evans and coworkers exploited the thermal rearrangement of diene 83 for preparation of the cw-decalin system 84, an intermediate in the synthesis of ( )-luciduline, a Lycopodium alkaloid. 

The corresponding A -piperideinium cation (41), probably the universal intermediate in piperidine, quinolizidine, and lycopodium alkaloid biosynthesis, is susceptible to nucleophilic attack much like its V-methyl-A -pyrrolinium cation counterpart in pyrrolidine and tropane alkaloid biosynthesis. Moreover, A -piperideine (40) might be reduced to piperidine (42), which now in turn might serve as nucleophilic species. For example, condensation of piperidine (42) with piperoyl-CoA catalyzed by piperidine V-piperoyltransferase (EC 2.3.1.145) yields piperine (43), the main alkaloid found in black pepper where it is responsible for the characteristic pungent taste. 

The tandem alkene metathesis reactions can also be combined with other types of transformation. One recent elegant example was reported by Mulzer and Ramharter et al. in their total synthesis of the Lycopodium alkaloid (+)-lycoflexine... 

There is no uniform classification for the A. In the literature divisions according to origin (examples Aconitum, Amaryllidaceae, Aspidosperma, cactus, Catharanthus, Cephalotaxus, Cinchona, coca, Corydalis, curare, Dendrobates, ergot, Erythrina, Iboga, Lycopodium, Maytenus, opium, Rauvol-fia, Senecio, Strychnos, tobacco, Vinca alkaloids, salamander, Solanum, Veratrum steroid alkaloids) in addition to divisions according to chemical structure (examples aporphine, benzylisoquinoline, bis-benzylisoquinoline, berberine, carboline, diterpene, inudazole, indole, indolizidine, isoquinoline, lupinane, macrocyclic, morphine, peptide, / -phenyl-ethylamine, piperidine, purine, pyridine, pyrrolidine, pyrrolizidine, quinoline, quinolizidine, quinucli-dine, spermine, spermidine, steroid, terpene, tro-pane, tropolone alkaloids) are used. 

Let s look at another alkaloid whose structure screams Mannich reaction for an endgame. Luciduline is one member of the Lycopodium family of alkaloids. This is a large family of natural products. A few structures are shown here (50-54). Luciduline (55) is a )8-aminoketone. This is precisely the difunctional relationship that results from the Mannich reaction. Thus, a strategy that passes through 56 en route to 55 seems likely to succeed. Aminoketone 56 is a 1,5-difunctional compound and, in principle, should be available using normal carbonyl chemistry. We will see an example of this later, but the first synthesis of luciduline approached 56 from 1,6-difunctional intermediate 57. One versatile method for the preparation of 1,6-dicarbonyl compounds is the oxy-Cope rearrangement. We saw this in the Evans synthesis of juvabione (Chapter 5) and indeed, this is the methodology used by Evans and Scott in their synthesis of luciduline (58 57). 

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