Vomilenine

The leaves of four New Caledonian Rauwolfia species, namely R. balansae ssp. balansae Boiteau, R. balansae ssp. schumanniana var. basicola Boiteau, R. spathulata Boiteau, and R. sevenetii Boiteau, contain vomilenine (102a), JVa-desmethyl-2-dehydrotetraphyllicine (102b), and raucaffrinoline (103), which have previously been encountered in other Rauwolfia species.736 The fourth alkaloid, l-desmethyl-2-dehydro-17-acetylajmaline (104), has been prepared by the oxidation of ajmaline, but has not previously been isolated from a natural source. 

FALKENHAGEN, H., STOCKIGT, J., Enzymatic biosynthesis of vomilenine, a key intermediate of the ajmaline pathway, catalyzed by a novel cytochrome P450-dependent enzyme from plant cell cultures of Rauwoljia serpentina. Z. Naturforsch., 1995, 50C, 45-53. 

VON SCHUMANN, G., GAO, S STOCKIGT, J., Vomilenine reductase - a novel enzyme catalyzing a crucial step in the biosynthesis of the therapeutically applied antiarrhythmic alkaloid ajmaline. Bioorg. Med. Chem., 2002,10,1913-1918. 

Significant efforts to select lines of R. serpentina that accumulate high levels of a heart drug known as ajmaline have failed since they tend to accumulate raucaffricine, the glucoside of vomilenine (Fig. 8.10). Cell cultures contain both a... 

In R. serpentina cell cultures, vomilenine is converted to its glycoside, rau-caffricine, and this has a very significant effect on ajmaline production. In... 

Taylor et al. (93) applied the reaction to the synthesis of dihy-drovomilenine (310), which is derived from vomilenine (311) on hydrogenation. LTA oxidation of diacetylajmaline (309) as above led to... 

O,O-diacetate (312). The former was identical with dihydro-vomilenine (Scheme 37). 

The writers suggest that raucaffriline, whose structure has not been conclusively determined (88a), may in fact be identical with Z-vomilenine (33). 

Compounds such as perakine (31) and raucafFrinoiine (35), with their rearranged maline structures, are now considered to be artefacts, formed from E-vomilenine (32) during the isolation process 166). 

Scheme 10. Hypothetical transformation of -vomilenine (32) via intermediates 32a/32b) to 19-epiperakine (31a) (C-19a-CH3).

Scheme 11. Transformation of Z-vomilenine (33), via intermediate 33a/33b chano form), to perakine (31).

Takayama et ci. (167b) have shown that bodi synthetic f vomilenine (32) and synthetic Z-vomilenine (33) are transformed to perakine (31), but the latter is transformed much faster and under less drastic conditions. This supports the assumption that perakine (31) is "directly" formed from Z-vomilenine (33) (vide supra), which is more or less totally "consumed" during the isolation procedure and which is thus difficult to detect as a naturally occurring alkaloid. 

A similar procedure starting from majorinine (10-medioxy- -vomilenine)... 

Sond., vomilenine has been obtained from the tissue culture... 

Of the several structures which were considered upon biogenetic grounds, one (Chart V) was found to be correct as the result of an X-ray crystallographic analysis carried out using peraksine methiodide. The drawings assume the same absolute stereochemistry as other type I alkaloids (2). Peraksine is thus closely related to the hypothetical proximal precursors of vomilenine and its isomerization product, perakine. 

Chart V. Some properties of peraksine, vomilenine, perakine, ajmaline, and isoajmaline. 

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