Ajmaline alkaloids structures

Several alkaloids are closely related to tetraphyllicine (XXVI, 21-deoxy-J i9-ajmaline), whose structure was proved (52) essentially by... 

Because of their close biogenetic relationship, earlier reviews (1-3) treated the ajmaline alkaloids together with the sarpagine alkaloids. The number of known structures in the two series has grown markedly, however, and to do this now would require a long and time consuming editorial process, which would diminish the relevance of the information udien published. For this reason, we prefer to treat the... 

The mass spectra of ajmaline type alkaloids can be divided into three main groups namely, ajmaline (17) and similar compounds widi a H-2P orientation, ajmalidine (15) and other compounds with a 17-keto group, and compounds with a H-2a configuration [e.g. quebrachidine (36)]. For the general features of the mass spectra of ajmaline alkaloids, and the determination of structures with the aid of mass spectra, see Refs. 198-202. 

As well as macralstonine71" and others, a new alkaloid,716 alstonisidine, has been isolated from Alstonia muelleriana. The structure (80) suggested for this dimer rests on spectral measurements, principally the presence of several ions in its mass spectrum which have the same mass numbers as characteristic fragment ions of authentic macroline and ajmaline alkaloids, the formation of a mono-0-acetate, of a triol with lithium aluminium hydride (fission of N—C—O), and the detection of formaldehyde after acid treatment. Formaldehyde was also detected after a model acid treatment of quebrachidine (81) and it is suggested that this rather surprising result can be explained, for both the dimer, believed to contain a quebrachidine unit, and for quebrachidine itself as shown [arrows in (81) and (82)]. 

The 3-hydroxyajmaline derivatives [e.g. herbamine (85) and herbadine (86) (4)], which exist, in part, in the 2-acylindolenine form, and thus behave in a different manner, are not included in this review (Scheme 1). The various alkaloids of the seco ajmalinoid type [e.g. rhazicine (87), isoihazicine (88) and sandwicoline (89) (4)] are also excluded from the present review (Figure 3). In addition, some doubtful compounds of unknown structures (e.g. sandwicensine and ajmaiinine), which have persisted in earlier lists of ajmaline alkaloids (i), have been rejected. 

Aldehyde 198 served as a key intermediate in a synthesis of the alkaloid ajmaline. The. Mannich aminomethylation transform triggers disconnection of two bonds in 198 to form dialdehyde 199, which by connective transform application can be converted to cyclopentene 200.58,59 The reduction in functional group reactivity and in structural complexity are both apparent by comparison of 198 and 200. 

The pair corynantheine-corynantheidine plays an important role in that a number of alkaloids of other structural types can be transformed into derivatives of either of this pair. The configuration a of C-15,H can thus be assigned to ajmaline (CXIII) because it can be transformed into two isomers of CXV, one of which on further transformation yields a tetracyclic derivative (CXV) related to corynantheidine (75). The same sequence of reactions applied to isoajmaline (epimeric at C-20 with ajmaline) gives a derivative of corynantheine (75). Sarpagine (CXVI)... 

Rauwolfia species have been the source of other bases closely related to ajmaline, and the structures of some of them can be regarded as trapped intermediates of the plausible, but as yet still hypothetical, biogenetic route to the major alkaloid, ajmaline itself. 

Forni described a method for quantitative determination of ajmaline in bark and root samples of Rauwoifia vomitoria. Because of the presence of many products in the raw methanoltc extract of the crude drug, an extraction of the acidified extract was performed with chloroform prior to extraction of the alkaloids with the same solvent after adjustment of the pH to 8.5. Because of the polarity of the alkaloids, they were silanized before gas chromatography on a 3 % 0V-17 on Chromosorb U column. A gas chromatogram showing the good separation of ajmaline from other alkaloids with similar structures and arbutin, which was used as an internal standard, is found in Figure 17.6. 

The number of known ajmaline structures sensu stricto) has grown markedly in recent years to a present count of 77 (compounds 1 - 77). Some of these might be artefacts and a few structures have not been convincingly determined vide in/m). In addition, seven bisindole alkaloids (compounds 78 84) containing at least one monomeric ajmalan unit have been isolated, increasing the total number to 84 (77 + 7). 

The quinuclidines (41) and, to a lesser extent, the iso-quinuclidines (42) have attracted considerable interest since they are themselves parts of alkaloids. The quinuclidine system is contained in the Cinchona alkaloids (43), in ajmaline (44) from Rauwolfia spp., and in macusine (45) obtained from Strychnos spp. The iso-quinuclidine ring structure occurs in the Iboga alkaloids (46) ... 

---