Rauvolfia species

Bracher, D. and Kutchan, T. M. 1992. Polymerase chain reaction comparison of the gene for strictoside synthase from ten Rauvolfia species. Plant Cell Reports, 11 179-182. 

R. serpentina cell cultures, raucaffricine levels amounted to 1.2 g/L medium, whereas ajmaline levels reached only 0.3 g/L medium (Schtibel et al, 1986). It is interesting to note that raucaffricine is a fypical constituent of R. cajfra, but has not been isolated from other Rauvolfia species. However, in Rauvolfia cell cultures the compound is found in all species tested, with a maximum yield in R. serpentina. In other words, under these growth conditions, the pathway to ajmaline appears to have become deregulated. 

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. 

Yohimbine Rauvolfia species, Corynanthe species 6.50 No data available ... 

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-... 

Biosynthesis The biosynthesis of these alkaloids begins with the key reaction, the condensation of tryptamine with secologanin to give strictosidine catalyzed by the enzyme strictosidine synthase. The biosynthesis was elucidated mainly by the use of plant cell suspension cultures. Cell cultures of Catharanthus and Rauvolfia species have been the subject of intense phytochemical studies. 

The previous pioneering work by Court and coworkers resulted in the most comprehensive phytochemical analysis of Rauvolfia species. For instance, during their work on 10 mainland African species, 133 individual indole alkaloids were identified. Moreover, recently eight new indole alkaloids have been isolated from Rauvolfia species of mainland China and the structures of them were identified by Liu and colleagues. Seven novel indole alkaloids from the leaves and twigs of Rauvoffia verticillata were also identified. ... 

Ajmalicine (7) was first isolated from yohimbe bark and, later, from Rauvolfia species. This compound is one of the principal alkaloids of Catharanthus roseus. Ajmalicine is found in members of both the Apocynaceae and Rubiaceae. Approximately 3600 kg are produced each year at a market price of about 2000/kg (Verpoorte et al., 1991). 

Court WE 1983 Alkaloid distribution in some African Rauvolfia species. Planta Med 48 228-233... 

Pooled fractions from several samples of curare also afforded mavacurine, fluorocurine, fluorocurinine, calebassinine, C-alkaloid Y (profluorocurine) and C-alkaloids L, M, and X [259,283]. These two alkaloids are not known to occur in Strychnos species and they pesumably came from an additive to the curare, perhaps a Rauvolfia species. 

Rauwolfia is the dried rhizome and roots of Rauwolfia (sometimes Rauvolfia) serpentina (Apocynaceae) or snakeroot, a small shrub from India, Pakistan, Burma, and Thailand. Other species used in commerce include R. vomitoria from tropical Africa, a small tree whose leaves after ingestion cause violent vomiting, and R. canescens = R. tetraphylla) from India and the... 

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). 

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

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... 

Rauvolfia, Vinca, and Strychnos species. Strictosidine (79) and 5a-carboxy-strictosidine (78) have been isolated from R. serpentina and S. nux-vomica and were characterized as the pentaacetate and the methoxycarbonyl pentaacetate derivatives, respectively. 

Y. is the main alkaloid of many Aspidosperma species, it also occurs in Rubiaceae such as Corynanthe johimbe i=Pausinystalia) and related trees as well as in some Apocynaceae (e. g., Rauvolfia and Vinca species). Y. is structurally related to the Rauvolfia alkaloids, e. g., reserpine. Y. is the methyl ester of yohimb(in)ic acid (C20H24N2O3, Mr 340.42, mp. 280-300°C). In medicine Y. is used especially in the form of its more water-soluble hydrochloride (decomp. at 302 °C) as a... 

When methyl jasmonate was applied to the surface of tomato plants, the synthesis of a defensive proteinase inhibitor protein was induced, not only in the plant to which the application was made but also in nearby plants. In subsequent studies, this compound was shown to have a similar effect with plants of other families as well (Farmer and Ryan, 1990 Pearce et al., 1991). In a series of experiments, it was demonstrated that methyl jasmonate can be a component of interplant communication systems. Octadecanoid precursors of jasmonic acid were able to activate the synthesis of wound-inducible proteinase inhibitors (Crombie and Mistry, 1991 Farmer and Ryan, 1992). Jasmonic acid is a signal transducer in elicitor-induced plant cultures of Rauvolfia canescens and Eschscholtzia californica. Tissue cultures of 36 species of plants could be induced to accumulate second-... 

The genus Rauvolfia (about 150 species from the tropics and subtropics) has long been used medicinally. Authenticated reports of the use of R. serpentina as a medicine date back to 1000 b.c. The hypotensive activity of die drug was reported in 1933. As indigenous supplies became depleted in India, the development of R. vomitoria, an African species, and R. tetraphylla, a Central American species, was carried out (Cordell, 1981 Tyler et al., 1981). Because the root of Rauvolfia serpentina contains more than 50 alkaloids, it is not surprising that the crude drug differs in activity from isolated reserpine (39) (Fig. 34.11) (Tyler et al., 1981). The crude drug contains from 0.15% to 0.20% alkaloids. 

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