Rhazya stricta

Heteronuclear two-dimensional /-resolved spectra contain the chemical shift information of one nuclear species (e.g., C) along one axis, and its coupling information with another type of nucleus (say, H) along the other axis. 2D /-resolved spectra are therefore often referred to as /,8-spectra. The heteronuclear 2D /-resolved spectrum of stricticine, a new alkaloid isolated by one of the authors from Rhazya stricta, is shown in Fig. 5.1. On the extreme left is the broadband H-decoupled C-NMR spectrum, in the center is the 2D /-resolved spectrum recorded as a stacked plot, and on the right is the con tour plot, the most common way to present such spectra. The multiplicity of each carbon can be seen clearly in the contour plot. 

Recently, Cordell and collaborators (51) reported the discovery of (—)-16-epi-(Z)-isositsirikine (48) from the leaves of Catharanthus roseus (L.) G.Don and Rhazya stricta Decaisne, the first isositsirikine-type alkaloid with Z geometry in the C-20 ethylidene side chain. Moreover, they gave reliable structure assignments for (-)-( )-isositsirikine (46) and (—)-16-epi-( )-isositsirkine (47). 

Akuammicine Catharanthus roseus Catharanthus ovalis Rhazya stricta... 

Morinda citrifolia / and officinalis Rhazya stricta Valeria officinalis... 

Lobelia inflata, mentat, Morinda citrifolia and officinalis, and Rhazya stricta have all been suggested to have antidepressant properties. There are no controlled studies, however, with any of these herbal products to support these claims. Moreover, these products are not innocuous. 

Rhazya stricta is a poisonous plant used as a traditional folk medicine in the United Arab Emirates. It has possible antineoplastic effects and may have considerable cytotoxicity. Although antidepressant activity has been suggested on the basis of animal studies ( 251), essentially no information on its pharmacology, efficacy, or safety in humans is available. 

Ali B, Bashir AK, Tanira MO. The effect of rhazya stricta decne, a traditional medicinal plant, on the forced swimming test in rats. Pharmacol Biochem Behav 1998 59 547-550. 

Rhazinilam 3 is an axially chiral phenyl-pyrrole compound which was first isolated from Melodinus australis (F. Muell.) Pierre [53]. It has also been found in other Apocynaceae such as Rhazya stricta Decaisne [54,55], Aspidosperma quebracho-bianco Schlecht. [56,57], Leuconitis eugenifolia A. DC [58,59] and Kopsia singapurensis [60]. More recently, (-)-rhazinilam was isolated from intergeneric somatic hybrid cell cultures of two Apocynaceae, Rauvolfia serpentina Benth. Ex Kurz and Rhazia stricta Decaisne [61]. 

The occurrence of geissoschizine in the leaves of Rhazya stricta has been confirmed,5Sa and it has also been isolated from Bonafousia tetrastachya.SSb... 

Rhazinaline, one of the minor alkaloids of Rhazya stricta, has been formulated55 as (167), i.e. 16-formyl-16-epistrictamine, and may well be identical with the alkaloid of this structure isolated earlier from the same source by Smith and his collaborators.95 However, it has not yet proved possible to compare the two specimens directly. 

Other alkaloids isolated from Rhazya stricta include96 strictamine (168) and strictalamine (169). The structure and relative configuration of strictamine were confirmed by X-ray crystal structure analysis strictalamine is then (169), since reduction of (168) and (169) affords the same primary alcohol (170), with retention of stereochemical integrity at C-17. Conversely, Oppenauer oxidation of (170)... 

In connection with the rearrangement of strictalamine to (-)-nor-C-fluoro-curarine (171), it is of interest to note that this latter compound has also been found96 to occur in Rhazya stricta a rearrangement of the type (169)— (171) may therefore provide a possible alternative mode of biosynthesis of (171) and aku-ammicine derivatives. 

By the use of mass spectroscopy coupled with deuterium labeling, eburnamonine, (iso (eburnamine, and ebumamenine have been shown to exist (stereochemistry not specified) in Rhazya stricta Decaisine, and ebumamenine itself in Aspidosperma quebracho bianco Schlecht (19). The obtention of ebumamenine from Pleiocarpa species is described in Section III. 

A number of alkaloids with the aspidospermine skeleton occur in the genus Vinca and are dealt with in detail in Chapter 12. They include the very important base vindoline (CIII) which not only occurs as the free base in Vinca rosea (= Lochnera rosea = Catharanthus roseus) but also as part of the dimeric alkaloids vinblastine (vincaleucoblastine) and leurosine, whereas the Aa-formyl analog, CIV, forms part of the dimeric alkaloid leurocristine (5, 72a). These dimeric alkaloids have been used successfully for the treatment of certain forms of cancer in man (5). Vindolinine (CVI) has also been isolated from V. rosea and its dihydro-decarbomethoxy derivative, tuboxenin (CVI-A), which is the parent member of the series, occurs in a Pleiocarpa species (53). ( + )-Vincadif-formine (XCIII, 6, 74) has already been mentioned as the racemic form of (— )-6,7-dihydrotabersonine (Section II, O). It has been found in V. difformis and in Rhazya stricta (51b) where the (+) form also occurs. 

Among the many alkaloids of Rhazya stricta (see Table I), the structure of the alkaloid rhazinine remains to be determined (197). This indolic base, C19H24N2O, contains a primary alcoholic group but, unlike akuammidine (CCCXXII) which accompanies it in the plant, it contains no G-methyl (197). Other alkaloids of the same plant include rhazidine, C20H26N2O3, H20, mp 278-279°, [[Pg.505]

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). 

Since oxidized derivatives of secodine appear to be involved as late intermediates in the biosynthesis of the aspidospermidine and pseudoas-pidospermidine alkaloids, it is logical to begin with those secodine derivatives that have been found to occur naturally. Tetrahydrosecodine (1) occurs in the root bark of Aspidosperma marcgravianum Woodson (5) and has been detected in cell-suspension cultures of Rhazya stricta Decaisne (6) its demethoxycarbonyl derivative (2) also occurs in A. marcgravianum (5), and in Haplophyton crooksii L. Benson (7,8) and the roots of R. stricta (9). The two isomeric carbonyl derivatives, 2-ethyl-3-[2-(3-acetyl-V-piperidino)ethyl]indole (3) and crooksidine (4), occur, respectively, in A. marcgravianum (5) and H. crooksii (7,8). 

Macro-isolation and radiochemical dilution analysis based upon the incorporation of [5- H]loganin proved that both vincoside and isovincoside are present in Vinca rosea plants, and N-acetylvincoside was also isolated. Independently and simultaneously with the above work, strictosidine was isolated from Rhazya stricta, was proved to be present by dilution analysis in... 

Strong support for the formation of (45) in the biological cleavage process came (a) from the isolation of tetrahydrosecodine (47) from Rhazya stricta and... 

The isolation and characterisation of vincoside " (39a), isovincoside " (39b), and N(4)-acetylvincoside from Vinca rosea, and of strictosidine [same overall structure as (39) but not yet stereochemically defined] from Rhazya stricta, have certainly provided the most exciting and significant new structures in this... 

---