Mitraphylline

Adina rubrostipulata K. Schumann. Mitraphylline i (rubradinine Denis). Mitragyna diversifolia Hook. Mitraversine. ... 

Mitraphylline 7-Hydroxyindolenine ajmalicine (66) Serpentine (40) Sitsirikine (48) Isositsirikine (58) + + ... 

Acacia catechu Willd. ErCha (Catechu, Jerusalem thorn) (peeled branch) d-Catechin, catechutanic acid, epicatechin, gambir-fluorescein, gambirine, mitraphylline, tannin, roxburghine I ).33-450 Promote salivation, resolve phlegm, stop bleeding, treat pyogenic infections. 

As Scheme (17) demonstrates, the isomerization of oxindoles may occur, at least in theory, at C-3 or C-7, or both. Originally, Wenkert and co-workers [44] suggested that it took place only at C-7, a conclusion they arrived at by examining the equilibration of formosanine (60), isoformosanine (61), mitraphylline (62) and isomitraphylline (63), Fig. 

In the oxindole group, formosanine and mitraphylline have been isolated from the bark of Uncaria elliptica R.B. ex G. Dm.,61a and rumberine (10-hydr-oxyisopteropodine) and palmirine (10-methoxyisopteropodine) from the aerial parts of Hamelia patens Jacq.616 Rauvoxinine has been reported14" to be present in the leaves of R. psychotrioides, but the identification rests mainly on its mass spectrum. 

The indole alkaloids of Mitragyna hirsuta Havil, M.javanica Koord. et Val. var. microphylla Craib, M. speciosa, and Nauclea coadunata are mostly in the corynantheine-heteroyohimbine-yohimbine group. The alkaloids isolated from the leaves of Mitragyna hirsuta have been identified as hirsutine, rhynchophylline, isorhynchophylline, mitraphylline, isomi-... 

The occurrence of alkaloids in Mitragyna species was first reported by Hooper, who isolated a crystalline alkaloid in 0.15% yield from the leaves of M. parvifolia (1) this alkaloid was not named and has not since been reinvestigated. The leaves of M. speciosa contain the amorphous alkaloid mitragynine, mp 105°-115° (2, 3), while the bark contains mitraspecine, C23H30N2O5, mp 244°-245°, [a]ff° -59.15° (4, 5). A third base, giving an amorphous picrate, mp 123°-127°, is also present, but this has not been studied further, since no crystalline derivatives could be obtained (6). The alkaloid mitraphylline, C21H24N2O4, mp 270°,... 

The pharmacology of these alkaloids has been discussed on numerous occasions (2, 3, 22, 23, 39-50). Mitragynine and, to a lesser extent, mitraphylline, exert a general depressant effect, and in some respects resemble cocaine (2, 3, 40, 44) mitraphylline is also a hypotensive (41). In connection with the use of Mitrogyna extracts as a febrifuge, it is of interest that rhynchophylline (mitrinermine) exhibits a significant antipyretic action (45, 46). The hypotensive effects of the total extracts (39) are, in part, owing to rhynchophylline (23). 

The presence of an oxindole nucleus in mitraphylline is established by the results of zinc dust distillation. The basic products include isoquinoline and 3,4-diethylpyridine, while the neutral fraction affords 3-spirocyclopropano-oxindole (IV), mp 179°-181° (55, 56). This degradation product is of the greatest importance in this series of alkaloids it was first obtained from the calcium oxide distillation of rhynchophyllic acid (19), and has since been obtained by zinc dust distillation of uncarine-A (58), by hydrogenation and pyrolysis of uncarine-A methiodide (59), and by zinc dust distillation of formosanine (uncarine-B) (60). The structure of this neutral degradation product was first proposed by Wenkert and Reid (61), who pointed out that its properties were very similar to those... 

The foregoing degradations, when considered in conjunction with the spectrographic properties of the molecule and the proved presence of one O-methyl group, resulted in the provisional formulation of mitraphylline as V, i.e., as the tetracyclic oxindole analog of ajmalicine (56). This expression was based on the molecular formula C21H26N2O4, and on the assumption that the molecule contains a carbomethoxy group. 

NHCH2), which exhibits a typical dihydroindole UV-spectrum, and which, in contrast to mitraphylline, couples with diazotized sulfanilic acid. The formation of a dihydroindole derivative, and not an indole derivative, in this reduction is an indication, though not perhaps a conclusive one, that the molecule is a 3,3-disubstituted oxindole hence, structure V is invalidated (57). 

Independently, Nozoye (10) also proposed structure VI for mitraphylline, on the basis of the identity of its UV-spectrum and the close similarity of its IR-spectrum (except in the fingerprint region) with those of formosanine (uncarine-B), for which the constitution VI had already been proposed. 

The stereochemistry of mitraphylline has been discussed, and divergent views have been expressed (10, 64, 65, 66) nevertheless, there is sufficient experimental evidence available now to allow configurational... 

Mitraphylline and isomitraphylline must accordingly differ in the configuration at C-3 and/or at C-7. 

These conclusions have received convincing confirmation in a partial synthesis of mitraphylline and isomitraphylline from ajmalicine (IX)... 

As in the case of mitraphylline, a re-examination of the available evidence, together with some new experimental data, led to the adoption of the constitution VI for uncarine-A and formosanine. Reduction of... 

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