Lycopodium alkaloids number

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... 

The hypothesis that the Lycopodium alkaloids were of polyketide origin was advanced by Conroy at a time when only a few alkaloids of this family were known 43). By suitable combination of two 3,5,7-triketooctanoic acid chains in conjunction with a nitrogen source it is possible to account for the structures of the alkaloids of Chart 1. With the exception of luciduline the manner in which the two chains are considered to combine is implicit in the numbering system adopted for these alkaloids carbons 1 to 8 comprise one chain and carbons 9 to 16 the other. 

Lycopodium alkaloids have attracted the attention of many natural product chemists and synthetic organic chemists due to their important biological activities and unique skeletal characteristics. A number of elegant total syntheses of many kinds of Lycopodium alkaloids have been reported in recent years (Fig. 9) (selected reports on the total synthesis of Lycopodium alkaloids by other researchers in recent years [28, 55-78]). In this review, we have shown that asymmetric total synthesis played a key role in elucidating the stmctures of these complex natural products. 

The structure of annotinine had just been established w hen the last review of the Lycopodium alkaloids appeared in this series (16). The intervening years have seen a remarkable expansion in our knowledge of these alkaloids. The number of alkaloids isolated and characterized has increased greatly as a result of the examination of new species and of the reexamination of other species using modern methods of separation. More spectacular, however, have been the advances achieved in the structural studies. In 1960, three years after the annotinine problem had been resolved, the structure of lycopodine was elucidated (17). In rapid succession, thereafter, structures were proposed and verified for - and -obscurine (18), lycodine (19, 20), selagine (21), and a number of alkaloids related in structure to lycopodine. 

The numbering system which is used throughout is that proposed by Wiesner (26) in his earlier review of the Lycopodium alkaloids. It is based on Conroy s polyacetate hypothesis of the biogenesis of these alkaloids from two straight-chain eight-carbon units (27). This system is applied in the formulas of Chart 1 which illustrates the principal ring systems known in this series. 

Dehydrogenation of cernuine over Pd-charcoal yielded 2-n-butyl-4-methyl-6-w-pentylpyridine in 10% yield, identified by comparison with a synthetic specimen. This product accounted for all but one of the 16 carbon atoms of cernuine. The biogenetic scheme proposed by Conroy (27) has been unusually successful in accommodating the Lycopodium alkaloids of known structure and when applied to this problem it led to structures CXLVI-A and CXLVI-B for cernuine and lycocernuine, respectively. The numbering system, adopted by Ayer et al. and shown in formula CXLVI, indicates how the two polyacetate units may be linked. Structures CXLVI-A and B are in accord with the spectral data of cernuine, lycocernuine, and their derivatives discussed above. The formation of 4-methyl-2-7i-butyl-6-m-pentylpyridine in dehydrogenation may be readily accounted for. Moreover, the two structures accounted for the major peaks found in the mass spectra of the two alkaloids. 

The structures of all Lycopodium alkaloids isolated thus far may be accommodated within the polyacetate biogenetic hypothesis proposed by Conroy 27) which has been alluded to in earlier sections of this review. His scheme proposes that the alkaloids are formed from two 3,5,7-triketooctanoic acid chains. The manner in which the two chains combine is illustrated by the numbering system proposed b " Wiesner (26) and adopted in this review. The odd-numbered C atoms represent the acetate carboxyl and the even-numbered C atoms the acetate methyl groups. This biogenetic scheme was put forward at a time when the structures of only a few alkaloids were known annotinine, lycopodine, a- and j8-obscurine, and selagine. It is perhaps more than coincidental that it also accommodates the novel structural types found in cernuine and serratinine. 

A number of new species of Lycopodium have been investigated and other species reinvestigated since the last review. The alkaloids and the species in which they have been found are listed in Tables I and II... 

Figure 27 Synthetic epimers of Lycopodium quinolizidine alkaloids 5-ep/-senepodine G (1159) 5-ep/-cermizine C (1160) (cermizine numbering).

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