Nortropane alkaloids

These are the group of alkaloids that possess a 8-methyl-8-aza-hicyclo [l,2,3]octane or tropane skeleton, e.g. atropine, cocaine and scopolamine. Tropane alkaloids occur mainly in plants from the families Solanaceae and Erythroxylaceae. 8-Aza-hicyclo[l,2,3]octane, i.e. tropane without the 8-methyl group, is known as nortropane. 

Goldmann, A., B. Message, D. Tepfer, R. J. Molyneux, O. Duclos, F. D. Boyer, and A. D. Elbein. Biological activities of the nortropane alkaloid, calystegine B2, and analogs structure-function relationships. J. Nat. Prod. 59 1137-1142. 

Molyneux RJ, Nash RJ and Asano N (1996) Chemistry and biological activity of the calystegines and related nortropane alkaloids. Alkaloids, Chemical and Biological Perspectives (ed Pelletier SW) Vol 11. Elsevier, Amsterdam, pp 303-343. 

Glycosidase-inhibiting alkaloids from plants are classified into five structural classes polyhydroxylated pyrrolidines, piperidines, indolizidines, pyrrolizidines, and nortropanes. Furthermore, they also occur as the glycosides. This review describes recent studies on isolation, characterization, glycosidase inhibitory activity, and therapeutic application of the sugar-mimicking alkaloids from plants. 

Tab. 5.1 Distribution of polyhydroxylated nortropane and indolizidine alkaloids in the Convolvulaceae. 

Figure 7. Some naturally-occurring polyhydroxylated nortropane alkaloids.

Bicyclo[3.2.1]octane (XXIII) has not been studied in detail, but the properties of the tropane alkaloids s are entirely consistent with the conformation XXIV for nortropane. The 1,6-anhydroglycopyranoses, such as... 

Both alkaloids have (+) and (-) forms but only the (-) hyoscyamine and (-) scopolamine are active. The biosynthetic pathway of tropane alkaloids, Fig. (1) is not totally understood, especially at the enzymatic level. Edward Leete has pioneered the biosynthetic studies of tropane alkaloid since 1950"s using whole plants and isotope labels [85-86]. The tropane alkaloid hyoscyamine is bioconverted by the enzyme H6H (hyoscyamine 6p-hydroxylase, EC 1.14.11.11) to scopolamine via 6p-hydroxyhyoscyamine. Hyoscyamine is the ester of tropine and (S)-tropic acid. The (S)-tropic acid moiety derives from the amino acid L-phenylalanine, while the bicyclic tropane ring derives from L-omithine primarily or L-arginine via tropinone. Tropinone is stereospecifically reduced to form either, tropine which is incorporated into hyoscyamine, or on the other hand into pseudotropine which proceeds to calystegines, a group of nortropane derivates that were first found in the Convolvulaceae family [87]. 

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