Of cathenamine

For the biosynthetic conversion of cathenamine (76) to the 19- and 20-epi derivatives, an equilibrium should exist between the enamine and imi-nium forms of cathenamine (i.e., 76 and 97) (767). This was examined (209) with deuterium labeling studies of incorporation into tetrahydro-alstonine (75), whereupon C-21 was labeled from both the enamine and iminium forms. When the enamine form was present, a second deuterium was incorporated (presumably at C-20) on reduction with NaBD DjO. Sulfate was effective in pushing the equilibrium toward the iminium species (209). 

Reduction of cathenamine with NaBD4 in D20 resulted in the incorporation of two deuterium atoms in the reduced product, tetrahydroalstonine131 (Scheme 96). 

Ajmalicine (raubasine) affects smooth muscle function and is used to help prevent strokes (93), and tetrahydroalstonine exhibits antipsychotic properties (Fig. 2d) (94). These compounds are found in a variety of plants, including C. roseus and R. serpentina. A partially purified NADPH-dependent reductase isolated from a tetrahydroalstonine that produces a C. roseus cell line was shown to catalyze the conversion of cathenamine, a spontaneous reaction product that results after strictosidine deglycosylation, to tetrahydroalstonine in vitro (95). A second C. roseus cell line contains an additional reductase that produces ajmalicine. Labeling studies performed with crude C. 

El-Sayed M, Choi YH, Frederich M, Roytrakul S, Verpoorte R. Alkaloid accumulation in Catharanthus roseus cell suspension cultures fed with stemmadenine. Biotech. Lett. 2004 26 793-798. Heinstein P, Hofle G, Stockigt J. Involvement of cathenamine in the formation of N-analogues of indole akaloids. Planta Med. 1979 37 349-357. 

It has been proposed that the biogenesis of the less abundant 19R heteroyohimbine alkaloids involves 1,4-addition of an enol to a Z-alkene, e.g. (76). A similar intermediate is presumably involved in the conversion of cathenamine (77a) into 19-epicathenamine (77b) by means of alumina in chloroform. 

The formation of ajmalicine from the carbinolamine or cathenamine requires a reduction. Hemscheidt (217) and Stdckigt et al. (222) described an enzyme cathenamine reductase (CR), which used cathenamine as substrate and NADPH as cofactor, yielding ajmalicine and 19-epi-ajmalicine. Hemscheidt and Zenk (223) reported partial purification of an NADPH-dependent tetrahydroalstonine synthase (THAS) from C. roseus cell cultures. This enzyme only yields tetrahydroalstonine, and the substrate was the iminium form of cathenamine. The Km for this substrate is 62 /nAf. The molecular mass of the enzyme was estimated to be 81 kDa. 

AjmaUcine is derived from hyptamine (partly from geraniol) via secologanin, strictosidine, and cathenamine. It has a Corynanthe skeleton from deglycosylated strictosidine [28]. AjmaUcine is synthesized in the cytosol by the action of cathenamine reductase on cathenamine facilitated by NADPH activity [32]. The biosynthesis of ajmalicine has been studied with reference to improving the cmitent by various biotechnological approaches (Fig. 20.4). The regulatirai per se of ajmalicine production has not been explored in larger detail. 

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