Quinolizidines dimeric

The synthesis of quinolizidine (3-spiro-2 )-tetrahydrothiophene (67a, 67b), a model compound for the synthesis of dimeric sulfur alkaloids, was reported (65, 66). The compound was prepared from 2-cyanotetrahydrothiophene (66) by two independent routes, both utilizing phase-transfer catalysis (Scheme 10). 

The previous review on Nuphar (water-lily) alkaloids in this treatise appeared in Volume 35, and covered the period 1974-1987 (7). It overlapped in part with the treatment of simple bicyclic Nuphar metabolites in Volume 28 (7). Nuphar alkaloids include sesquiterpenoid monomeric (C15) piperidine and quinolizidine alkaloids as well as more complex dimeric (C30) sulfur-containing metabolites. Related metabolites isolated from the scent glands of the Canadian beaver, Castor fiber, also include a unique indolizidine alkaloid 944 606). Only the indolizidine and simple quinolizidine alkaloids are relevant to the present review. Compounds mentioned in the ensuing discussion are illustrated in Fig. 18. 

Indole and isoquinoline alkaloids continue to play a dominant role. The apor-phinoids, comprising proaporphines, aporphines and related dimers, are treated separately, partly in order to reduce the burden on contributors aristolactams and aristolochic acids, which have not been reviewed since 1961, also are discussed in this chapter. This year the quinolizidine alkaloids, including the sesquiterpenoid Nuphar bases and the appropriate Lythraceae alkaloids, as well as azaphenalenes of plant and insect origin are reviewed together. Amaryllidaceae, Erythrina, imidazole, purine and peptide alkaloids are omitted from this volume, but it is expected that the chemistry of these groups covering the period 1974—1976 will be surveyed in Volume 7. 

Quinolizidine alkaloids are derived from lysine. Studies with labeled precursors indicate that a symmetrical intermediate, cadaverine (20), is involved in their formation (Herbert, 1988 Kinghom and Balandrin, 1984 Leete, 1983 Spenser, 1985), although no intermediate comparable to the dimeric form plays a role in the formation of pyrrolizidine alkaloids is involved (Spenser, 1985). Much recent information is based on cell suspension cultures of Lupinus polyphyllus, Baptisia australis, and Sarothamnus scoparius (all Faba-ceae). Lysine decarboxylase is localized in leaf chloroplasts (Wink 1987 Wink and Hartmann, 1982,1984) the presence of a diamine oxidase does not appear to be involved. Lysine decarboxylase is found in all parts of Lupinus plants. 

While for developing of simple piperidine alkaloids, e.g., pelletierine (Punica granatum), piperine (Piper nigrum et longum), and lobeline (Lobelia inflata), only one molecule of lysine is necessary, for quinolizidine alkaloids - e.g., lupinine (Lupinus luteus), sparteine of antiarrhythmic activity (Sarothamnus scoparius), and cytisine of respiratory stimulant effect (Laburnum species) - two molecules of lysines are indispensable. It was also proved that lycopodine (Lycopodium tristachyum, clubmoss) of quinolizidine structure has no polyketide origin, but it is a modified dimer of pelletierine, which, in turn, is derivable from lysine and acetate. 

Kobayashi, M., Miyamoto, Y, Aoki, S., Murakami, N., Kitagawa. 1., In, Y, and Ishida, T. (1998) Marine natural products. XXXIX. Isomerization of dimeric 2,9-disubstituted 1-oxa-quinolizidine alkaloids and structural revision of araguspongines B and E from a marine sponge ofXestospor a sp. Heterocydes, 47,195—203. 

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