Alkaloids polyhydroxy

Polyhydroxylated Alkaloids. Polyhydroxy derivatives of pyrrolidine, piperidine, and indolizidine alkaloids have recently been isolated from plants and microorganisms. A number of these compounds have shown potent gluco-sidase inhibitory activity and have generated interest because of their ability to inhibit replication of retroviruses. 

Reductive coupling of the corresponding nitrones with alkyl acrylate is the key step in the short synthetic route of the selective and irreversible GABA inhibitor of amino transferase (S)-vigabatine (534) and of polyhydroxy pyrrolizidine alkaloid (+ )-hyacinthacine A2 (535). 

Dipolarophiles D14. The 1,3-dipolar cycloaddition of nitrones to dimethyl maleate and dimethyl fumarate is widely used in the synthesis of polyhydroxy alkaloid derivatives of dihydroindolizidinone (81), pyrrolizidine (119), (—)-codonopsinine, and (+ )-hyacinthacines Ai and A2 (312). In cases of unstable nitrones, syntheses of cycloadducts are performed in situ (81). 

Steroidal Alkaloids and Steroidal Glycoalkaloids Norditerpenoid Alkaloids Pyrrolizidine Alkaloids Indolizidine and Polyhydroxy Alkaloids Tropane Alkaloids Glycosides... 

Polyhydroxy alkaloids have considerable potential for treatment of a variety of disease states in humans and animals. The challenge to using them as commercial drugs is to minimize their toxicity and enhance the specificity of their beneficial effects. 

Molyneux, R.J., James, L.F., Ralphs, M.H., Pfister, J.A., Panter, K.E. and Nash, R.J. (1994). Polyhydroxy alkaloid glycosidase inhibitors from poisonous plants of global distibution Analysis and identification, in Colegate, S.M. and Dorling, P.R., Eds., Plant-associated toxins agricultural, phytochemical and ecological aspects, CAB International, Wallingford, pp. 107-112. 

Scofield AM, Fellows LE, Nash RJ, Fleet GWJ. (1987) Inhibition of mammalian digestive disaccharidases by polyhydroxy alkaloids. Life Sci 39 645-650. 

Elbein, A. D. and Molyneux, R. J. 1987. The chemistry and biochemistry of simple indolizidine and related polyhydroxy alkaloids. In Alkaloids Chemical and Biological Perspectives. Vol. 5 (Pelletier, S. W ed.), pp. 1-54. New York Wiley-Interscience. 

Some areas where ortho esters have found use involve the elucidation of the structure proof of polyhydroxy alkaloids [4-8], the protection of the esterified hydroxyl groups during chemical transformations of the other parts of the molecule [9], the area of pharmacological screening [10], and the preparation of novel polymers [11]. 

This Chapter is designed to review the chemistry and biological activity of the calystegines, which at the present time are rarely found to occur in association with the correspondingly substituted tropane alkaloids. However, new sources of calystegines are rapidly bong discovered and die occurrence of additional polyhydroxy tropane alkaloids cannot be excluded. 

These compounds were originally named as "calystegins" but the term "calystegines has subsequently been adopted by certain research groups. In order to conform with the more usual convention for naming of alkaloids and to emphasize their relationship to other polyhydroxy alkaloids, the latter term will be used throughout this Chapter. 

Calystegines, in common with other classes of polyhydroxy alkaloids, are highly water-soluble and cannot be isolated by conventional alkaloid separation techniques which employ add-base pardoning methods with non-hydroxylic organic solvents [20], Ion-exchange chromatography is therefore extensively employed for separation of the alkaloid fraction from neutral and addic compounds present in the extract [21,22]. 

In situations when analysis is required to establish the presence and identity of calystegines in a plant extract it is not necessary to utilize a complex series of chromatographic separations. The plant material can be extracted with methanol or methanol-water and passage over a Dowex 50W-X8 column with dilute ammonium hydroxide as eluant provides substantial purification, yielding the alkaloid fraction, including other polyhydroxy alkaloids, contaminated only by basic amino adds. The extract can thus be rapidly prepared for analysis [29,30]. 

Lallemand s group has also investigated an alternative route to the crucial aminocycloheptanone intermediate (46) via a Diels-Alder addition between an acylnitroso derivative (44) and a protected polyhydroxy-cycloheptadiene (45) [56]. Due to an inability to remove the allyl groups chosen for protection of the hydroxyl functionality, this approach has yielded a propyl ether derivative of calystegine B2 other protecting groups which can be removed with more facility should render the parent alkaloid accessible. 

RJ Molyneux, Polyhydroxy indolizidines and related alkaloids. In Methods in Plant Biochemistry Volume 8 - Alkaloids and Sulphur Compounds, PG Waterman, Ed., Academic Press, London, 1993, pp. 511-530. 

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