Ajmaline alkaloids

The ajmaline alkaloids have been reviewed only twice in "The Alkaloids" series (1,2). Both articles appeared in the sixties and are substantially out-of-date. The need for a new review in the series is apparent. A review article in the series "Progress in the Chemistry of Natural Products" (3) was published in 1983, but even that will soon be twenty years old. Yearly summaries have been compiled by Saxton (4) and short reviews have occasionally appeared in connection with other topics (5-9). The present chapter covers the literature to October, 1999. 

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 NMR spectral data for ajmaline alkaloids are presented in Table III. High-field data are reported where available, but for some alkaloids only older data measured with low-field techniques were available. Despite the incompleteness of the older data they were judged to be useful for comparison and are therefore included in Table III. Caution is nevertheless needed in utilizing the older data, as they often contain errors. 

In the mid-eighties, Lounasmaa et a/. (189) measured and interpreted the high field NMR spectra of twelve basic ajmaline alkaloids. Several earlier erroneous signal assignments were corrected in the process. 

The quebrachidine subgroup alkaloids (e.g. alkaloids 36 and 43) are easily distinguished from the otiier ajmaline alkaloids by die C-2H doublets Hz)... 

NMR spectroscopy has permitted many stereochemical problems with the ajmaline alkaloids to be solved (e.g. 78, 82b, 121, 191-197). In addition, identical NMR spectral data of two alkaloids, together with identical optical rotations, would iqipear to provide the best and most rapid way to establish the... 

As with the NMR spectra vide supra), there has been much confusion in the literature over the NMR spectra of ajmaline alkaloids (78, 82b). Although many errors have been corrected (192, 193), caution is still needed, especially in utilizing earlier spectral data. 

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. 

Several cardenolide derivatives of ajmaline alkaloids have been synthesised and tested for their anti-arrhythmic activity. iV(,-(Strophanthidin-3 -yloxycarbonyl mediyl)ajmalinium chloride (167) was found to be one of die most potent of these (210). 

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 general role played by strictosidine (151) (Fig. 8) in the biosynthesis of all monoterpenoid indole alkaloids is firmly established (220-224). In the biogenetic formation of sarpagine (and ajmaline) alkaloids, the van Tamelen proposal (201,202) has been generally accepted (213,222,223), that is, that formation of a bond between C-5 and C-16 in the intermediate 4,5-... 

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... 

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