Ajmaline alkaloids synthesis

N-Acyliminium ions as intermediates in alkaloid synthesis, 32, 271 (1988) Ajmaline-Sarpagine alkaloids, 8, 789 (1965), 11, 41 (1968)... 

This intermediate was used to prepare several indole alkaloids of the ajmaline-sarpagine group [333]. The method has also been used to synthesize examples of the fumitremorgin group [334]. Lewis has summarized application of these and other methods to alkaloid synthesis [335]. 

Total Synthesis of Sarpagine-Related Ajmaline Alkaloids 162... 

Total Synthesis of Sarpagine-Related Ajmaline Alkaloids 5.5.7 Stereocontrolled Total Synthesis of (-)-Vincamajinine (291)... 

The rearrangement has occurred stereospecifically from the desired a-face of the double bond to provide optically active 73, presumably via a chair transition state (Eq. 3.1.46) [58]. This rearrangement has significant imphcations for the enantiospecific synthesis of the macroHne/sarpagine/ajmaline alkaloids, because... 

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. 

During the enantiospecihc total synthesis of ajmalin-related alkaloids, (-)-suaveoline and (-)-raumacline, N-debenzylation of the hydrochloride salt of the alkaloids was performed with 10% Pd/C (0.12 mol Pd/mol compound) in absolute EtOH at room temperature and 1 atm of hydrogen for 1 or 2 hours. When this catalytic debenzylation was performed, however, using 10% Pd/C (0.28 mol Pd/mol compound) in MeOH for 5 hours, N-methyl derivatives were produced in good yield (Scheme 4.91).339,340... 

A-Acyliminium ions are versatile intermediates for synthesis of nitrogenous compounds, particularly alkaloids [154]. The conjugate system is very electrophilic such that it can be intercepted by various donors including carbonyl compounds and jt-systems. In comparison with a,p-unsaturated ketones the replacement of the a-carbon with a nitrogen atom accentuates the reactivity of these species. Ingenious applications of the JV-acyliminium ions include service to synthesis of corydaline [155], lycoramine [156], quebrachamine [157], and ajmaline [158], to name a very few. 

Synthesis of the anti-arrhythmic drug ajmaline from Rauvolfia plants, an efficient source of several alkaloid types used in therapy, represents an even more advanced study of the total enzymatic synthesis of terpenoid indole alkaloids. Ajmaline is a class I anti-arrhythmic alkaloid because of its activity as heart muscle sodium channels antagonist [35],... 

There are a large number of alkaloids that contain the quinuclidine nucleus such as the sarpagine, ajmaline and cinchona families. The quinuclidines 1-3 have been used for the synthesis of such alkaloids. They have pharmacological activities. Thus, several reports have highlighted the potential of chiral hydroxylated quinuclidines in propping the active site of muscarinic receptors. Substituted quinuclidines may provide selective Vaughan Williams class 111 antiarrhythmic effects. " ... 

A formal total synthesis of ajmaline has been accomplished. Most of the alkaloids can be interconverted with the exception of a general method for preparing 2-acylindoles from their ring-closed equivalents. Some progress has been made toward this goal (3), dihydroburnamicine being the synthetic closest to a natural product. 

Oxidation of 3,3-disubstituted indoline derivatives (121) with 5 equiv of H202 H2NC0NH2 complex in the presence of a catalytic amount of Na2W04 (82b) also affords the A a-hydroxyoxindole derivatives (118) in moderate yield (84a). By applying this procedure, the synthesis of a new humantenine-type alkaloid, 20-hydroxydihydrorankinidine (26), starting from ajmaline (66) was achieved (84b). 

The spectroscopic data for a new alkaloid 8 (6) showed a similarity to those reported for anhydrovobasinediol (taberpsychine) (10) 11,12), but a significant NOE observed between H-19 and H-15 in the H-NMR spectrum of 8 suggested that the configuration of the ethylidene side chain was in the Z form. The C-NMR signal due to C-15 of 8 was observed downfield (7.0 ppm) and, in contrast, that of C-21 was observed upheld (6.9 ppm) compared to the corresponding signal of 10. The structure of 8 inferred by spectroscopic analysis to be 19(Z)-anhydrovobasinediol was confirmed by chemical synthesis from ajmaline (Section II.B). 

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