Ajmaline structure

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). 

In a recent paper, Lounasmaa and Hanhinen (204) presented evidence to suggest that the bond formation between C-5 and C-16 takes place not after, as had been generally accepted (222-224), but before the D-ring formation (151 - 155— 156, Scheme 20). Once intermediate 156 is formed, transformation to sarpagine (and eventually to ajmaline) structures can take place by normal biogenetic routes (e.g., 156—> 157 —> 158, Scheme 21). 

The complexity of the ajmaline structure makes it difficult to identifying its biosynthetic pathway. The solution to this problem is an in-depth elucidation of each reaction step and each enzyme involved in the catalysis." This article reviews the relevant research on the ajmaline s main biosynthetic pathway and its side routes, the route beyond ajmahne, the application of in vivo NMR, the chemo-enzymatic significance of the involved enzymes and, their reaction mechanisms and the enzyme X-ray crystal stmctures. 

Compounds such as perakine (31) and raucaffrinoline (35), with their rearranged ajmaline structures, are now considered to be artefacts, formed from E-vomilenine (32) during the isolation process (166). 

Scheme 18. The Lounasmaa and Hanhinen proposal for the bond fonnation between C 5 and C-16 in the transformation of strictosidine (149) into saipagine structures [represented by 16-ep/-vomilenine (154)] and ajmaline structures [represented by vinorine (22)].

Altogether this means that in the general biogenetic formation of monoterpenoid indole alkaloids possessing the unrearranged skeletal system (173-175), the route leading to the sarpagine and ajmaline structures takes a course of its own (159 —> 157 158 —> 154 —> 22) before the formation of 4,21-... 

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. 

Therapeutic Function Antiarrhythmic Chemical Name Ajmalan-17,21-diol, (17R,21a)-Common Name Ajmaline Rauwolfine Structural Formula ho... 

Mechanism of action. Na -channel blocking antiarrhythmics resemble most local anesthetics in being cationic amphiphilic molecules (p.206 exception phenytoin, p.191). Possible molecular mechanisms of their inhibitory effects are outlined on p.202 in more detail. Their low structural specificity is reflected by a low selectivity toward different cation channels. Besides the Na channel. Carotid 1C channels are also likely to be blocked. Accordingly, cationic amphiphilic antiarrhythmics affect both the depolarization and repolarization phases. Depending on the substance, AP duration can be increased (Class IA), decreased (Class IB), or remain the same (Class IC). Antiarrhythmics representative of these categories include Class IA—quinidine, procainamide, ajmaline, disopyramide Class IB—lidocaine, mexile-tine, tocainide Class IC—flecainide, propafenone. 

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. 

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

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. 

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... 

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