Biosynthesis ajmaline alkaloids

Ruppert, M., Xueyan, M. and Stockigt, J. (2005) Alkaloid biosynthesis in Rauvolfia-cDNA cloning of the major enzymes of the ajmaline pathway. Curr. Org. Chem., 9, 1431-44. 

The general role played by strictosidine (151) (Fig. 8) in the biosynthesis of all monoterpenoid indole alkaloids is firmly established (220-224). In the biogenetic formation of sarpagine (and ajmaline) alkaloids, the van Tamelen proposal (201,202) has been generally accepted (213,222,223), that is, that formation of a bond between C-5 and C-16 in the intermediate 4,5-... 

Terpenoid Indole Alkaloids.—Important recent work has defined strictosidine (97) as a key intermediate in the biosynthesis of terpenoid indole alkaloids with both 3a- and 3/3-configurations. Some of this work, published earlier in preliminary form (cf. Vol. 9, p. 18), is now available in a full paper.26 In addition to those alkaloids examined earlier, strychnine, gelsemine, vincadifformine, isoreserpiline, aricine, isoreserpinine, and ajmaline have been shown to derive from strictosidine (data are also included for ajmalicine, for catharanthine, and for vindoline which had been reported earlier). 

SCHMIDT, D., STOCKIGT, J., Enzymatic formation of the sarpagan-bridge A key step in the biosynthesis of sarpagine- and ajmaline-type alkaloids. Planta Med., 1995,61,254-258. 

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. 

Stockigt J. Enzymatic biosynthesis of monoterpenoid indole alkaloids ajmaline, sarpagine and vindoline. Studies Organ. Chem. 1986 26 497-511. 

Pfitzner A, Stoeckigt J. Biogenetic link between sarpagine and ajmaline type alkaloids. Tetrahedron Lett. 1983 24 5197-5200. Gerasimenko I, Ma X, Sheludko Y, Mentele R, Lottspeich E, Stockigt J. Purification and partial amino acid sequences of the enzyme vinorine synthase involved in a crucial step of ajmaline biosynthesis. Bioorg. Med. Chem. 2004 12 2781-2786. 

Gao S, von Schumann G, Stockigt J. A newly detectedreductase from Rauvolfia closes a gap in the biosynthesis of the antiar-rhythmic alkaloid ajmaline. Planta Med. 2002 68 906-911. 

Hie first, by Lounastnaa and Hanhinen, updates an area of indole alkaloids which has been neglected in the series for over 30 years, namely, the ajmaline group of alkaloids, where numerous advances in chemistry and biosynthesis have been made recently. The second chapter by Michael reports on the progress made in a vast area of alkaloid chemistry, those alkaloids with either an indolizidine or a quinolizidine nucleus derived from plant, marine animal, and fungal sources. 

Protein biosynthesis is essential for all cells and thus provides another important target. Indeed, a number of alkaloids have been detected (although not too many have been studied in this context) which inhibit protein biosynthesis in vitro. Emetine from Cephaelis ipecacuanha (Rubiaceae) is the most potent plant constituent other alkaloids with the same ability include harringtonine, homoharringtonine, cryptopleurine, tubulosine, hemanthamine, lycorine, narciclasine, pretazettine, pseudolycorine, tylocrepine, and tylopherine [5] and furthermore, ajmaline, berberine, boldine, cinchonine, cinchonidine, harmalin, harmin, lobeline, norharman, papaverine, quinidine, quinine, salsoline, sanguinarine,... 

The biosynthesis of ajmaline is illustrated as an example for the biosynthesis of a monoterpenoid indole alkaloid (see flgure). tit Pelletier 1, 2U-376. 

Biosynthesis R. is derived from vomilenine, an intermediate in the biosynthetic pathway to the antiarrhyth-mic ajmaline, by glucosylation. The corresponding glucosyl transferase is membrane-bound, dependent on uridine diphosphate glucose, and has a high substrate specificity. A soluble, substrate-specific glu-cosidase effects the reversal of this reaction see also Rauvolfia alkaloids. 

The enzyme-catalyzed biosynthesis of the sarpagan-ajmalan-type firni-ihes of monoterpenoid indole alkaloids in the genus Rauvolfia, in particular R. serpentina Benth. ex Kurz, have recendy been delineated in detail. The major pathway leading to the structural intricate antiarrhythmic ajmaline, together with several side routes and bypasses, form a comprehensive and complex anabolic network of which a multitude of single-enzymatic... 

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