Alkaloids oxindole

The humantenine-type Gelsemium alkaloids, which so far include human-tenine, humantenirine, and rankinidine, are oxindole alkaloids with a novel skeleton similar to that of gelsemine but lacking a bond between C-6 and C-20. From a biogenetic viewpoint, humantenine-type alkaloids are less evolved than those of the gelsemine series and might well be immediate precursors of them... 

One might set the hypothesis that intestinal disturbances, which are a common syrup-tom in depression, could be the result of a serotonin-like mechanism because the Horsfieldia species, including Horsfieldia superba (Hk. f. et. Th.) Warb., are known to elaborate unusual series of oxindole alkaloids, such as horsfiline (9). 

Jossang AP, Jossang HA, Hadi H, Bodo B. Horsfiline, an oxindole alkaloid from Hors-fieldia superba. J. Org. Chem 1991 56 6527. 

Only three examples of ibogan-type oxindole alkaloids are known, and two of them, crassanine (156) and tabemoxidine (155), were found in Tabernaemon-tana. Crassanine (C23H30N2O5, MP 191°C, [a]D +21°) was isolated in minute amounts by Cava et al. from T. crassa (79). Its IR spectrum indicated the presence of two carbonyl groupings (1739 and 1709 cm - ), while its UV spectrum was almost superimposable on that of known 10,11-dimethoxyoxindoles such as kisantine (200). In addition to the carbomethoxy methyl at 3.47 ppm and two aromatic methoxyls at 3.83 ppm (6H), the H-NMR spectrum of 156 exhibited two singlets (1H) at 6.50 and 7.01 ppm and the low-field oxindole NH at 9.30 ppm. The latter values are similar to those recorded for kisantine, and on this basis Cava et al. proposed the structure 102 for crassanine. To date, no evidence is available on the configuration at the C-7 spiro center. 

The conversion of indole alkaloids to oxindole derivatives has been studied extensively. Since this review does not deal with the literature of oxindole alkaloids, only the most important transformations of the alkaloids having indo-loquinolizine as well as yohimbane skeletons are to be mentioned. 

Wurm, M., L. Kacani, G. Laus, K. Keplinger, and M. P. Dierich. 1998. Pentacyclic oxindole alkaloids from Uncaria tomentosa induce human endothelial cells to release a lymphocyte proliferation regulating factor. Planta Med. 64 701-704. 

ABSTRACT The acid-catalysed epimerization reaction of bioactive indole alkaloids and their derivatives is reviewed. The three mechanisms, which have been proposed for the (J-carboline-type indole alkaloids, are discussed. Through recent developments, evidence for all three mechanisms has been obtained, which shows the complexity of the epimerization reaction. The epimerization seems to depend on structural features and reaction conditions making it difficult to define one universal mechanism. On the other hand, the isomerization mechanism of oxindole alkaloids has been widely accepted. The acid-catalysed epimerization reaction provides a powerful tool in selectively manipulating the stereochemistry at the epimeric centre and it can also have a marked effect on the pharmacology of any epimerizable compound. Therefore, examples of this reaction in die total synthesis of indole alkaloids are given and pharmacological activities of some C-3 epimeric diastereomers are compared. Finally, literature examples of acid-catalysed epimerization reactions are presented. 

An isomerization reaction closely similar to that observed with indole alkaloids has been noted with oxindole alkaloids. Due to their facile isomerization, it is pharmacologically difficult to test the individual oxindole isomers expected to have different activities. Instead of epimerization the term isomerization has been used with oxindole alkaloids since inversion of configuration can occur in more than one asymmetric centre. Isomerization was employed mainly to provide structural proof of different oxindole epimers isolated in nature. As early as 1959, Wenkert and co-workers [42] proposed a mechanism for the isomerization of oxindole alkaloids, Scheme (17). Almost simultaneously, Seaton et al. [43] reported analogous findings. 

Hence, it was concluded that epimerization of oxindole alkaloids with a trans D/E ring junction results in only C-7 epimers, whereas that of oxindole alkaloids with a cis D/E ring junction can result in C-7 and C-3 epimers [47]. The conclusion was based on steric and conformational considerations. 

Studies with corynantheine-type oxindole alkaloids have also been conducted [48]. Since rhynchophylline (68) and isorhynchophylline (69), Fig. (17), have an H-15 and H-20 trans relationship, epimerization would be expected to occur only at C-7. And indeed, this proved to be the case acetic acid treatment yielded a ratio of 70 30 (68 69). Even though... 

Further evidence in favour of the mechanism depicted in Scheme (17) was obtained by showing that quatemization inhibits the isomerization of oxindole alkaloids [50]. The result is plausible enough, since participation of the Nb lone pair is a prerequisite for the mechanism. 

Oxindole alkaloids exhibit interesting pharmacological properties. However, due to their isomerization behaviour, it is extremely difficult to compare the pharmacological effects of pure oxindole alkaloid isomers, and therefore an equilibrated mixture of isomers is often used instead [68]. 

The isomerization mechanism of oxindole alkaloids, in contrast, has never caused confusion. The mechanism, proposed independently by Wenkert and Seaton, has been accepted throughout the literature. 

About a dozen l-methoxy-2-oxindole alkaloids have been isolated and identified, either by X-ray crystallography or by sophisticated spectroscopy. Most are associated with their des-l-methoxy analogues in the plants. Very little chemistry involving the l-methoxy-2-oxindole ring system of these compounds has been done, and they will therefore be considered only briefly. 

Carletti I, Banaigs B, Amade P (2000) Matemone, a New Bioactive Bromine-Containing Oxindole Alkaloid from the Indian Ocean Sponge Iotrochota purpurea. J Nat Prod 63 981... 

In the elucidation of the stereochemistry about C(7) in the oxindole alkaloids the chemical shifts of the 9-proton and of the 14ax-proton are of importance. Thus in the spectrum of cabucine oxindole A (IS) [399]... 

A 400 MHz n.m.r. study640 of the eight parent heteroyohimbine alkaloids has permitted the chemical shifts of all the protons to be established. Carbon-13 n.m.r. data have also been recorded646 for the alio- and epiallo-oxindole alkaloids containing a heterocyclic ring E. 

The marine mollusc Nerita albicilla was found to contain an oxindole alkaloid that was identified as isoteropodine (91), a previously known plant metabolite (94), by extensive NMR spectroscopic techniques (95). Four indole derivatives, named polyandrocarpamides A-D (92-95), were isolated from the colonial ascidian Polyandrocarpa sp. collected in the Philippines (96). 

Kamano, Y., Zhang, H., Ichihara, Y., and Kizu, H., Convolutamydine A, a novel bioactive hydroxy-oxindole alkaloid from marine bryozoan Amathia convoluta, Tetrahedron Lett., 36, 2783, 1995. 

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