Ajmalicine group, synthesis

The UV-spectrum of mitragynine differs notably from the spectra of the other Mitragyna alkaloids. Whereas the absorption of the latter indicate the presence of oxindole nuclei, the spectrum of mitragynine shows a greater resemblance to that of the ajmalicine group of alkaloids (5). The presence of an indole nucleus is also suspected from its color reactions (2) and confirmed by the isolation of indole derivatives (so far unidentified) and 5-methoxy-9-methylharman (I) from the products of zinc dust distillation (6). The identification by synthesis (51) of this degradation product is of some interest, since the alkaloid itself does not apparently contain an iV-methyl group. Moreover, this was the first demonstration of the occurrence of a 4-hydroxyindole derivative in nature. 

The stereochemical assignments for the cyclization of 25.1 were based on conversion into synthetic intermediates for the synthesis of (— )-ajmalicine (25.6), (— )-tetrahydroalstonine (25.7), and ( — )-(10K)-hydroxydihydroquinine (25.8). No details of the stereochemical assignment of 25.5 were reported. These results can be rationalized by transition state 25.9, which allows for association of the donor and acceptor portions of the substrate. Attack occurs from the face of the enamine opposite to the phenyl group. As in the intermolecular reactions of similar imines, these reactions are probably under kinetic control. 

Compound 10 has also been used for the synthesis of (-)-ajmalicine (1) by epimerization of the methyl group at C-19 to afford 13, which underwent intramolecular cyclization to give 14. The stereogenic center at C-3 and the methoxycarbonylation at C-16 were created as mentioned above to give 15, which underwent reduction, dehydration and N-deprotection to produce 1. 

The formation of the monoterpenoid indole alkaloid ajmalicine (7) and its isomers from tryptamine (1) and secolo-ganin (2) involves the formation of four key intermediates (Fig. 34.2) (Hutchinson, 1986). Ajmalicine represents the first major stage in the synthesis of most major groups of monoterpenoid indole alkaloids (see below). Stereoselective... 

Ring Oxygen Heterocycles. The isomeric bases ajmalicine and tetrahydroalstonine (along with their tetradehydro compounds, serpentine and alstonine) are the most well known members of this group and had to be closely related to the seco compounds since upon dehydrogenation they yielded alstyrine. From the empirical formulae, absence of an isolated double bond, presence of C-methyl and a /3-oxyacrylic ester moiety (saponification and ultraviolet absorption spectra) the structures of ajmalicine and alstonine were derived. The stereochemical problems were not completely resolved until the total synthesis of ajmalicine was accomplished. 

Recently, the Hoffman-La Roche group reported an efficient convergent synthesis of ajmalicine, in which the D/E-rings of the molecule have been constructed from ffons-3-vinyl-4-piperidine acetic acid. ... 

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