Tropane alkaloids precursor feeding

Besides tropic and phenyllactic acids, little is known about the biosynthesis of other acids esterifying the tropane nucleus. Leete [26] listed the acids found in tropane alkaloids whose biosynthesis has been studied, usually by feeding labelled precursors to intact plants. Thus, tiglic acid, the acidic moiety of tigloidine and meteloidine, has been shown to be derived from the amino-acid L-isoleucine, probably via 2-methylbutanoic acid [38],... 

Production can be increased by addition of precursors to the culture media, in which cases the precursors are not metabolized in the medium and, after uptake, appear in the right compartment of the plant cell. For C. roseus cultures, for example, it was found that increased indole alkaloid production was obtained after feeding with L-tryptophan, tryptamine, secologanin, loganin, loganic acid, or shikimic acid (20). Cell cultures have also been used for biotransformations, for example, the conversion of (-)-codeinone to (-)-codeine in Papaver somniferum cultures (100). For the tropane alkaloids a large number of precursor feeding and biotransformation studies with cultures of various solanaceous plants have been performed (see below). 

Roeder E, Neuberger V (1988) Pyrrolizidinalkaloide in Symphytum-Art n. Ein Beitrag zum qualitativen und quantitativen Nachweis. Dtsch Apoth Ztg 128 1991-1994 Simola LK, Martinsen A, Huhtikangas A, Jokela R, Lounasmaa M (1989) Feeding experiments with precursors of tropane alkaloids using suspension cultures of Atropa belladonna. Acta Chem Scand 43 702-705... 

Feeding experiments have also been performed with more advanced putative precursors both for cocaine and tropane biosynthesis. In these experiments, the role of (21) and (22) in cocaine and tropane biosynthesis was examined. No incorporation of the ethyl ester derivative or of the N-acetylcysteamine thioester derivative of (21) into either of the alkaloids, cocaine or scopolamine, was observed [39]. However, isotope dilution experiments did provide evidence for the presence of (21) in Erythroxylon coca [46]. In the case of (22), fed as its ethyl ester, substantial specific incorporations into cocaine [47] and scopolamine [48] were recorded. These results were interpreted as corroborating evidence for the hypothesis that the acetate units in these alkaloids are introduced in a stepwise fashion via Path D2 in Scheme 8 with (22) as an intermediate. 

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