Lycopodium alkaloids, series

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. 

The isolation, characterization, biological activity, and biogenesis of the Lycopodium alkaloids were described in comprehensive surveys in Volumes 61 and 72 of this series of monographs, the latter dealing more particularly with synthetic h hhghts. In the interests of brevity, the information and syntheses covered in these two chapters will not be repeated in the present account. Three other recent reviews of the Lycopodium alkaloids are valuable for their summaries of isolation and structural characterization, ... 

The influence of solvents [64] and comparisons with catalysts of the diarylpro-linol series [65] were reported. For theoretical calculations on stereocontrol see Reference [66]. In addition, imidazolidin-4-one catalyzed cycloadditions have been used in several total syntheses of natural products. Intramolecular Diels-Alder reactions (IMDA) were reported as key steps in the synthesis of bicyclo-undecenes [67], amaminols [68], solanapyrones [69], telomerase inhibitor UCS1025A [70], englerin A [71], (-)-nor-platencin [72], and muironolide A [73]. In addition, asymmetric [3-1-2]-cycloadditions of azomethines were accomphshed in the presence of chiral imidazoUdinones [74]. Intermolecular cycloadditions of dihydropyridine 53 and acrolein catalyzed by imidazolidin-4-ones were reported. The chiral azabicyclo-octenol 54 was isolated as the important key intermediate in the total synthesis of lycopodium alkaloids [75] (e.g., ludduline) and oseltamivir (Scheme 4.19) [76]. 

Dauben, W.G., Rocco, V.R, and Shapiro, G., Intramolecular [2 + 2]-photocycloaddition of 4-substituted cyclopent-2-en-l-ones,/. Org. Chem., 50, 3155-3160,1985 Dauben, W.G., Sapiro, G., and Luders, L., Intramolecular [2 -I- 2]-photocycloaddition of 4-(aUenic-substituted)-2-cycloalken-1-ones. Ring size, length of side chain and temperature effects, Tetrahedron Lett., 26, 1429-1432, 1985 Weisner, K., On the stereochemistry of photoaddition between a,(3-unsaturated ketones and olefins. Tetrahedron, 31, 1655-1658, 1975 Weisner, K., Musil, V., and Weisner, K.J., Syntheses in the series of lycopodium alkaloids. IX. Two simple stereospecific syntheses of 12-epi-lycopodine, Tetrahedron Lett., 5643-5646, 1968. 

The first chapter, by Kobayashi and Morita, is a superb extension of the chapter that was published in Volume 45 of the series. It is a comprehensive review of the Lycopodium alkaloids in terms of their structural classification, distribution, and occurrence, followed by detailed discussions of their spectroscopic aspects, the determination of stereochemistry, and their biological activities. The substantial efforts made in the past few years to effect the synthesis of the diverse skeleta of this group of alkaloids from the club mosses are also presented, together with a detailed overview of their complex biogenetic interrelationships. 

In a series of insightful papers, Castillo and MacLean established that the club mosses Lycopodium magellanicum and Lycopodium paniculatum produce alkaloids possessing structural features distinctively different from other metabolites known to arise from these and related sources. The three members of this small and unique subset were identified to share in common a central bicyclo-[3.3.0]octane unit to which a functionalized cyclohexane and an N-methylpiperidine ring were laterally fused. The occurrence of magellanine (1) [2],... 

Volume 10 in the series "The Alkaloids" edited by R.H.F. Manske appeared of which almost half was devoted to the steroid alkaloids of the Solanum and Veratrum groups. The remainder includes sections on Rrythro-phleum, lycopodium, benzyllsoquinollne. Indole and Taxus alkaloids. 

A series of lycoposerramines isolated by Takayama et al. were fawcettimane-type and fawcettidane-type alkaloids from the same species Lycopodium serratum in Japan which contains huperzines in China. The structure of lycoposerramine-A (21), which has a l,2,4-oxadiazolidin-5-one residue in the molecule, was elucidated through spectroscopic data and X-ray analysis (31,32). Seven new alkaloids, lycoposerramines B (22), C (23), D (24), E (25), P (26), Q (27), S (28), and U (29), with novel, fawcettimine-related structures were isolated from the club moss Lycopodium serratum in Japan (33). Their relative and absolute stereochemistries were analyzed by spectroscopic data. X-ray analysis, and chemical correlations. The skeleton of lycoposerramine A (21) may be constructed by the incorporation of NH3, NH2OH, and a Ci unit into a fawcettimine-type skeleton. 

---