Oxindole-type alkaloids

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... 

For reasons of brevity, some skeletal variations are not clearly defined in Figs. 2 and 3 and some have been omitted. In particular, the picraline (Volume VIII, p. 147), the echitamine (Volume VIII, p. 174) 78), and the aspidodasycarpine 53) skeletons have been merged into type If. The new alstophylline type 39, 40) is somewhat hidden in the Id reprepresentation. Gelsemine (Volume VIII, p. 95) has been included in the oxindole type Ic. Type Ila Iboga) includes several closely related rearranged alkaloids (Volume VIII, Chapter 9) which are not shown in Fig. 3. An unusually modified Aspidosperma structure 83) is related to type III6 and is listed as such. 

Humantenine-type alkaloids are the oxindole derivatives of the C/D ring-cleaved sarpagine-type indole alkaloids. Only three humantenine-type JVa-methoxyoxindole alkaloids, i.e., humantenine (86) (7,49-52), humanteni-rine (87) (49,51,52), and rankinidine (88) (52), had been reported up to... 

Hydroxyrankinidine (90), which was determined by single-crystal X-ray analysis (53), and 11-hydroxyhumantenine (91) are the first Gelsemium oxindole alkaloids with a phenol group, although some other oxindole alkaloids have an 11-methoxy group. iSvo A a-desmethoxy humantenine-type alkaloids 92 (55) and 93 (54) were also found in nature for the first time. 20-Hydroxy-dihydrorankinidine (95), which was determined by... 

Biogenetically, the humantenine-type oxindole alkaloids would be generated from the sarpagine-type alkaloids such as 19(Z)-anhydrovobasinediol... 

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. 

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. 

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... 

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