Humantenine-type alkaloids

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 

Recently, nine new humantenine-related alkaloids 89-97 were isolated from G. elegans Benth. (Fig. 5). 

11-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 

X-ray analysis (54), and 15-hydroxyhumantenine (94) (54) are the very few members with a hydroxy group at the C-20 or C-15 positions among the Gelsemium oxindole alkaloids. Among these alkaloids, 87, 92, 93, and 95 were synthesized from relatively simple indole alkaloids (Section IV.B). 

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

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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... 

Humantenine-type Alkaloids from Gelsemium Species... 

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 next requirement for the synthesis of humantenine-type alkaloids was the development of a general synthetic procedure to prepare the TVa-... 

Scheme 16. A biogenetic route for the humantenine-type alkaloids.

Natural a-alkyhdene-S-lactams are almost unknown. Very recently, a new humantenine-type alkaloid, gelegamine B 19, was isolated from Gdsemium degan, a liane growing in Southeast Asia (Figure 4.3) [31]. Cytotoxicity of this compound was tested against H L-60 human leukemia and A-549 human lung cancer cell hnes, but no obvious effects were noticed. 

Only three humantenine-type AT a-methoxyoxindole alkaloids, humantenine (17), humantenirine (18) and rankinidine (19), from the Gelsemium species have been reported up to 1988. Recently, nine humantenine-related new alkaloids (20) - (28) were isolated from Gelsemium elegans Benth (Table 4). 

Biogenetically, the humantenine-type oxindole alkaloids would be generated from the sarpagine-type compounds such as 19(Z)-anhydrovobasinediol (6) through p-oxidation of the indole portion and subsequent rearrangement to the oxindoles (Fig. 13). 

By employing the newly developed methods, humantenirine (87), a representative humantenine-type Gelsemium alkaloid, was synthesized from a sarpagine-type indole alkaloid (63). The oxindole derivative 103 prepared from gardnerine (28) was used for further transformation (Scheme 20). 

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