Rauvolfia alkaloids

Classification based on botanical origin of the alkaloids are also used, e.g., Papaver (opium) alkaloids. Cinchona alkaloids, Rauvolfia alkaloids, Catharan-thus alkaloids, Strychnos alkaloids. Ergot alkaloids, cactus alkaloids, and Solanum alkaloids. The structures of some alkaloids are shown in Figure 1. 

Ruppert, M., Panjikar, S., Barleben, L. and Stockigt, J. 2006. Heterologous expression, purification, crystallization and primary X-ray analysis of raucaffricine glu-cosidase, a plant enzyme specifically involved in Rauvolfia alkaloid biosynthesis. Acta Crystallographica Section F-Structural Biology and Crystallization Communications, 62 257-260. 

Bracher, D. and Kutchan, T. M. 1992. Strictosidine synthase from Rauvolfia serpentina Analysis of a gene involved in indole alkaloid biosynthesis. Archives of Biochemistry and Biophysics, 294 717-723. 

Reserpine Alkaloid Antihypertensive (reduces blood pressure) Rauvolfia serpentina (Indian snakeroot)... 

N.A. Rauvolfia serpentina (L.) Benth. Indole alkaloids, reserpine, rescinnamine, ajmaline, yohimbine.99 Regulate hearbeat, treat high blood pressure and anxiety. Sedative and depressant effect on sympathetic nervous system. 

Within the natural products field, the investigation of complete biosynthetic pathways at the enzyme level has been especially successful for plant alkaloids of the monoterpenoid indole alkaloid family generated from the monoterpene gluco-side secologanin and decarboxylation product of tryptophan, tryptamine [3-5]. The most comprehensive enzymatic data are now available for the alkaloids ajmalicine (raubasine) from Catharanthus roseus, and for ajmaline from Indian Rauvolfia serpentina [6] the latter alkaloid with a six-membered ring system bearing nine chiral carbon atoms. Entymatic data exsist also for vindoline, the vincaleucoblastin (VLB) precursor for which some studies on enzymatic coupling of vindoline and catharanthine exist in order to get the so-called dimeric Catharanthus indole-alkaloids VLB or vincristine [7-9] with pronounced anti-cancer activity [10, 11]. 

Synthesis of the anti-arrhythmic drug ajmaline from Rauvolfia plants, an efficient source of several alkaloid types used in therapy, represents an even more advanced study of the total enzymatic synthesis of terpenoid indole alkaloids. Ajmaline is a class I anti-arrhythmic alkaloid because of its activity as heart muscle sodium channels antagonist [35],... 

Thirty-six plant species tested in cell suspension culture could be elicited by exogenously supplied methyl jasmonate to accumulate secondary metabolites by a factor of 9 to 30 over the control values. Induction by MJ was not specific to any one type of secondary metabolite but rather general to a wide spectrum of low molecular weight substances ranging from flavonoids, guaianolides and anthraquinones to various classes of alkaloids [96]. Endogenous jasmonic acid and its methyl ester (MJ) accumulate rapidly and transiently after treatment of plant cell suspension cultures of Rauvolfia canescens and Eschscholtzia califor-nica with a yeast elicitor [97]. 

Isolation of the stereospecific strictosidine s)mthase (STS) and formation of strictosidine with the 3a-(S) configuration proved conclusively that this was the natural precursor of the terpenoid indole alkaloids. Strictosidine occurs naturally in Rhazya stricta and the synthase has been isolated from a number of other species Amsonia salicifolia, A. tabemaemontam, Catharanthus pusillus, C. roseus, Rauvolfia verticillata, R. vomitoria, R. serpentina, Rhazya orientalis and Voacanga africana. The enzyme has been purified to homogeneity from R. serpentina (Hampp and Zenk, 1988). A comparison of the activity of STS from C. roseus roots, the only portion of the plant to contain ajmalicine, with that present in plant cell cultures producing the same alkaloid demonstrated that the plant cell cultures are far more metabolically active (Ziegler and Facchini, 2008). 

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. 

Gerasimenko I, Sheludko Y, Ma X, Stockigt J. Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a biosynthetic key to over 2000 monoterpenoid indole alkaloids. Eur. J. Biochem. 2002 269 2204-2213. 

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. 

After deglucosylation, the pathway proceeds through a 4,21-Dehydrogeissoschizine derivative to ajmalicine (an a-Blocking spasmolytic agent, used for tinnitus and cranial trauma with an ergot derivative). If cyclization occurs between C-17 and C-18, the yohimbine nucleus is produced, whose derivatives include the Rauvolfia alkaloids reserpine and resdnnamine (antihypertensive activity). Ajmaline, formerly used as an antiarrythmic, also occurs in Rauvolfia species, and several of the enzymes in the pathway have been isolated. Recent considerations suggest that the C-16-C-5 bond may be formed before the N-4-C-21 bond (Fig. 38). 

AJMALINE The alkaloid ajmaline is isolated from the root of Rauvolfia serpentine and other Rauvolfia species, family Apocynaceae (see section C02, Antihypertensives). Ajmaline has a very similar mode of action to quinidine. It works through retardation of the speed of depolarisation and repolarisation as well as a retardation of the reactivation of the sodium-system. Its sedative effect is weak. 

RAUVOLFIA-ALKALOIDS These have an interesting history. The Indian species Rauvolfia serpentine (L.) Benth. ex. Kurtz,... 

According to their mode of action the Rauvolfia-alkaloids can be divided into two gronps the centrally acting reserpine, rescinnamine, and deserpidine and the peripherally acting yohimbine, raubasine and ajmaline. The blood pressure lowering effect is dne to an inhibition of the sympathomimetic effects in the autonomic nervous system and has a long latency and duration. The effect is dne to depletion of the serotonin and... 

In their studies on the biosynthesis of terpenoid indole alkaloids, De Silva and co-workers have carried out a screening of some indole alkaloid producing plants of Sri Lanka for the occurrence of the first nitrogenous monoterpenoid precursor (70,71). In this survey, Rauvolfia serpentina, Strychnos nux-vomica, Cinchona ledgeriana, and a number of Mitragyna and Vinca species were tested for the presence of vincoside and 5a-carboxyvincoside. Although these two proposed bio-intermediates (at the time) were not detected, macroisolation techniques revealed the occurrence of 5a-carboxystrictosidine (78), an isomer of 5a-carboxyvincoside, in all plants tested, and strictosidine (79), an isomer of vincoside, only in... 

In the mid-1950s, A. Chatteijee and co-workers (197) isolated, initially from Rauvolfia serpentina and then from R. perakensis, an indoline alkaloid, which they called rauvolfinine and for which they claimed the structure 90 (Fig. 3). However, the data presented for structure 90 are somewhat vague and most would apply to the indoline alkaloid structure in general. It is noteworthy that other research groups have not yet been able to reisolate rauvolfinine (89). In our opinion, the observations concerning the existence and structure of rauvolfinine are erroneous. Probably, as pointed out by Taylor (1), the isolated samples consisted of impure mixtures of alkaloids, in which isoajmaline (91) may have been the main component (Fig. 4). 

In a paper appearing in 1984, Nasser and Court describe the isolation of several indole alkaloids from Rauvolfia caffra (15). For one of these... 

In 1959 Rao and co-workers (200) isolated from Rauvolfia micrantha a minor alkaloid, which they called neosarpagine and for which they proposed... 

Rauvolfia alkaloids are prepared in 0.5% alcoholic solution, and 10(l1 is applied for TLC, e.g. reserpine, rescinnamine, rauwolscine, ajmaline, serpentine. 

Ethyl acetale-methanol-water (100 13.5 10) Screening system, suitable e.g. for xanthine derivatives, Colchicum and Rauvolfia alkaloids... 

UV-365 nm Blue, blue-green or violet fluorescence of alkaloids, e.g. Rauvolfiae radix, Chiilac cortex, Ipecacuanhae radix, Boldo foliiini. Yellow fluorescence, e.g. colchicine, sanguiiiarine, berberine... 

Three alkaloids from Rauvolfia species have industrial interest aj-maline (38), reserpine (39), and rescinnamine. Ajmaline is used for its antiarrhythmic activity, reserpine and rescinnamine for their antihyper-... 

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