Convolvulaceae nortropane alkaloids

Tropane alkaloids (TAs), a class of specialized metabolites with a bicyclic tropane ring in their structures, include clinically important hyoscyamine and scopolamine, the stimulant and narcotic cocaine, and the nortropane alkaloids calystegines. Plants producing TAs are distributed, sometime sporadically, across separate angiosperm families (e.g., Proteaceae, Convolvulaceae, Brassicaceae, Euphorbiaceae, Rhizophoraceae, Solanaceae, and Erythroxylaceae) (Griffin and Lin 2000). Studies of TA biosynthesis have been performed predominantly in Solanaceae plants, and thus little is known regarding TA pathways in other families. 

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

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]. 

Since simple aromatic esters of 3a-hydroxytropane/-nortropane are absent in the Solanaceae family [the only exception (datumetine from Datura metel) can be interpreted as a convergence], these T3-type alkaloids occurring throughout many tribes of the Convolvulaceae can be considered as apomorphic characters of this family. 

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