Rhazya stricta, alkaloid

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). 

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)... 

E. Some Minor Alkaloids of Aspidosperma quebrachoblanco and Rhazya stricta... 

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). 

Sewarine, from Rhazya stricta, was shown to be 10-hydroxyakuammicine (66a) by spectral comparison with akuammicine (66b) and with other a ring oxygenated indole alkaloids. " Preakuammicine (67a), an isomer of precondylocarpine (67b), has been isolated from young Vinca rosea seedlings. " The retroaldol loss of formaldehyde and the formation of akuammicine was base catalysed. Boro-hydride reduction, as well as causing some retroaldolisation, gave rise to stemmadenine (65). 

Even closer to the postulated biogenetic intermediate are the structures of a group of alkaloids isolated from Rhazya stricta and/or R. orientalis. These are four monomers,derivatives of secodine (SD) (125a), and two dimeric groups, one based on presecamine (126) and the other on secamine " (127). ... 

A number of terpenoid indole alkaloids have pharmaceutical interest. These alkaloids are isolated from plants belonging to the families Apocy-naceae, Loganiaceae, and Rubiaceae. For the production of alkaloids by means of plant cell cultures, plants of the latter two families have proved to be rather recalcitrant (e.g., see Cinchona alkaloids). On the other hand, it has been reported by Pawelka and Stockigt that all apocynaceous cell suspensions they studied did produce terpenoid indole alkaloids 588). Here we confine ourselves to alkaloids which have direct commercial interest the production of new, potentially interesting, compounds is not reviewed here. For this we refer the reader to reviews by Balsevich (589), van der Heijden et al. (tribe Tabernaemontaneae) (590), and Omar (Rhazya stricta) (591). 

Strictosidine (104) is produced by the plant Rhazya stricta. A crude enzyme preparation from the plant was used to produce labelled strictosidine this, when incubated with Catharanthus enzyme, again gave the three alkaloids (105), (106), and (107). ° Cell-free preparations of cell-suspension cultures of Amsonia tabernaemontana, Rhazya orientalis, and Vinca minor were also observed to convert (102) plus (103) into strictosidine (104) with fair efficiency the formation of vincoside (109) was never observed. ... 

Mariee NK, KhaUl AA, Nasser AA, Al-Hitti MM, Ah WM. Isolation of the antimicrobial alkaloid stemmadenine from Iraqi Rhazya stricta. J Nat Prod 1988 51 186-7. 

Figure 4 Additional indole alkaloids produced in intergeneric hybrid cell suspension cultures of Rauvolfia serpentina x Rhazya stricta after treatment with methyljasmonate. ...

Rhazya stricta Decaisne (Apocynaceae) is a small shrub, growing profusely near Karacl It is used in the indigenous system of medicine as a bitter tonic, for soar throat and fever. We have previously reported twenty new alkaloids from it (ref.3). Recently we ha isolated three new indole alkaloids rhazizine (11), 15-3 hydroxyvincadifformine (12) a bhimberine acetate (13). 

Plant Cells. The metabolism of unlabelled alkaloids in plant cell cultures has been followed using heteronuclear multiple quantum coherence NMR. The addition of ajmaline to cell suspension cultures of somatic hybrids of Rauvolfia serpentina Benth. ex Kurz and Rhazya stricta Decaisne (R x R cells) resulted in its conversion to raumacline. When, vinorine, an intermediate of ajmaline metabolism, was added to suspensions on R x R cells, vellosimine was formed and then converted to 10-deoxysarpagine. However, vinorine was apparently metabolised by a second pathway to vomilenine or raucaffricine." ... 

Schnoes H K, Burlingame A L, Biemann K 1962 Application of mass spectrometry to structure problems. The occurrence of eburnamenine and related alkaloids in Rhazya stricta and Aspidosperma quebracho bianco. Tetrahedron Lett 993 - 999... 

Rhazya stricta Apocynaceae Root, stems, leaves and flowers Alkaloids Khan et al. (2004)... 

Three new Rhazya alkaloids possessing the general structure of a hypothetical intermediate which could bridge the major types of Indole alkaloids have been obtained from R. stricta and R. orientalis tetrahydro-(4) and dihydrosecodine (5) from the first species, and tetrahydrosecodine (by dilution analysis)and tetrahydrosecodin-17-ol (6) from the second. 

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