Alstonine

Alstonia constricta F. Muell. Alstonine (chlorogenine), alstonidine,... 

Most of these barks also contain considerable quantities of unnamed and uncharacterised amorphous alkaloids. The barks fall into three groups as sources of (a) alstonine, only found in A. constricta (b) villalstonine, found in Nos. (2) to (4) and (c) echitamine, isolated from Nos. (5) to (11). It is unusual to find species belonging to the same genus divided into such well-marked groups, in respect of their alkaloidal constituents. 

HjO) and Bj. H2SO4.4HjO, m.p. 203-4°, [a] ° + 120° the acid sulphate, B. HjSO, occurs in yellow prismatic needles, m.p. 246-8° (corr., dec.), [a]n + 113-1° (HjO) the hydrochloride forms yellow, pentagonal plates, m.p. 286° (corr., dec.), and shows a purple fluorescence in solution in alcohol the picrate separates from alcohol in rosettes of reddish-orange needles, m.p. 194-5° (cort.). Dilute solutions of the salts are yellow and show a marked blue fluorescence. Alstonine behaves as a monoacidic base, contains one methoxyl but no methylimino group, and, unlike echitamine, does not give indole colour reactions. 

Leonard and Elderfield have also carried out degradation experiments with alstonine and its tetrahydride. On fusion with potassium hydroxide at 300-350° in nitrogen, alstonine furnishes barman (p. 490) and indefinite basic and acidic fractions. Tetrahydroalstonine on like treatment produces barman, worharman, and three unidentified bases, each of which fluoresces blue in alcoholic hydrochloric acid Base A, C4,H4gN2, m.p. 171-5 to 172-5°, forms a picrate, m.p. > 267° is probably a substituted -carboline. Base B, or 18 3, gives apicrate, m.p. 261° (dec.). Base C,... 

On thermal decomposition of alstonine at 300-330°, the bases produced distilled at l20-170°/0-15 mm., and on fractionation as picrates gave three products Base D, C4,HigN2, picrate, m.p. 254-6°. Base E, C18H20N2, or CjgHgaNj, picrate m.p. 193-5-195°, not identical with Sharp s alstyrine, and base F, Cj3Hi2N2, m.p. 79-81°, pierate, m.p. 261-262-5°, hydrochloride, m.p. about 275° (dec.), methiodide, m.p. 283-4° (dec.). Base F has an ultraviolet absorption spectrum very similar to that of 2-ethyl- -carboline, but it is not that substance nor is it 1 2-dimethyl-/3-carboline, 2 3-dimethyl-j3-carboline, 1-ethyl- -carboline or 3-ethyl- -wocarboline. Base F was also produced when alstonine was distilled with zinc dust. 

All Hesse s alkaloids aeeompanying alstonine are amorphous except alstonidine, needles, m.p. 181°, whieh also yields crystalline salts, but for whieh no formula has been suggested. 

A number of pentacyclic quaternary j8-carbolinium derivatives undergo reactions in which the hetero ring is cleaved. Thus semper-virine (286) is converted in poor yield into the indole derivative 287 on catalytic hydrogenolysis with Raney nickel. Alstonine and serpentine yield the analogous product on treatment with selenium. 

Methoxy-3,4,5,6-tetradehydrocorynantheol (286), 3,4,5,6,18,19-Hexade-hydroochropposinine (287), 3,4,5,6-Tetradehydrositsirikine (288), Alstonine (289), the no-name-alkaloid (290) (Mitragyna speciosa) (98T8433), 3,4,5,6-Tetradehydropalicoside (291) and its methylester which were isolated recently from Strychnos mellodora (99P1171), Serpentine (292), and Serpentinine (293) are known representatives of this class of alkaloids. 

For the biosynthetic conversion of cathenamine (76) to the 19- and 20-epi derivatives, an equilibrium should exist between the enamine and imi-nium forms of cathenamine (i.e., 76 and 97) (767). This was examined (209) with deuterium labeling studies of incorporation into tetrahydro-alstonine (75), whereupon C-21 was labeled from both the enamine and iminium forms. When the enamine form was present, a second deuterium was incorporated (presumably at C-20) on reduction with NaBD DjO. Sulfate was effective in pushing the equilibrium toward the iminium species (209). 

In 1957, this approach was applied for the first time simultaneously by Mayer,4 Boyd,5 and Los, Saxena, and Stafford6 to an extensive group of heterocyclic compounds that can be considered analogs of the aromatic hydrocarbons of the azulene series.7,8 To express the general relationship among these compounds, they were classified by the term pseudoazulenes. Even then a number of such products existed,1 -9 36 but correlations involving this classification were not made. Instead, the investigation of these compounds was predominantly stimulated by the fact that the alkaloids sempervirine, alstonine, serpentine, and cryptolepine have pseudoazulene-type structures. 

The transformation to the 1,2,3,4-tetrahydro derivatives is best accomplished by hydrogenating the 2-alkyl-p-carboline salts in methanol adjusted to pH 10 with potassium hydroxide, as shown for alstonine hydrochloride (37) (eq. 12.65),124 or hydrogenating the anhydronium base in methanol, as shown with 2-methylharman (38) (eq. 12.66).125... 

Aside from alstonine, which was the only fully characterized base, these alkaloids were of doubtful homogeneity. In a careful examination of A. constricta bark, Sharp (7) confirmed the presence of alstonine and obtained it pure, and also isolated three further alkaloids, alkaloids A, B, and C, which could not be definitely identified with Hesse s alkaloids. More recently, a second pure base, alstoniline, has been isolated (8). The difficulty of isolating pure crystalline bases from this material was owing to their susceptibility to atmospheric oxidation this was not appreciated by the earlier workers, but it frustrated their attempts to obtain satisfactory duplication of experimental results. 

The bark of A. spectabilis R.Br. was extracted by Hesse (23, 31), who obtained ditamine, echitamine, echitenine, and alstonamine, the last-named being possibly identical with Scharlee s alstonine, isolated some years earlier. 

The third group of Alstonia species contains neither the alstonine nor the echitamine series of alkaloids hence, the genus appears to be divided into three clearly defined sections as far as alkaloid content is concerned. A. macrophylla Wall, contains villalstonine (33, 35), macralstonine (33, 36), macralstonidine, a base M which was obtained in minute amounts only (33), and macrophylline (37). A. villosa Blume contains villalstonine and base V, insufficiently characterized (33) A. somersetensis F. M. Bailey contains villalstonine and macralstonidine (33). 

From these observations no unequivocal conclusion could be reached concerning the identity of the chromophore which absorbs at 250 m/x, nor the function of the third oxygen atom. However, the presence of a /3-carboline system was accepted, in which Nb was substituted and Na was unsubstituted the latter accounted for the presence of one active hydrogen in tetrahydroalstonine. Since alstonine hydrochloride absorbs at higher wavelengths than 2-ethyl /3-carboline hydrochloride, it was assumed to possess greater conjugation, and the partial structure II was therefore proposed for alstonine (49). 

The isolation of /3-carboline derivatives and alstyrine from the degradation of alstonine suggests that the alkaloid contains the ring system IV to this must be added the chromophores, the ester group, and the third, unidentified, oxygen atom. Since the UV-spectrum of alstonine is very... 

The IR-data are also consistent with these conclusions. Twin maxima at 1695 and 1613 cm 1 are exhibited by tetrahydroalstonine, coryn-antheine, tetrahydroserpentine, and the model substance VIII, all of which possess the chromophore, ROOC—C=C—OR these are not observed in the spectra of VII and the saturated pyran derivatives (55). The formula X for alstonine also explains all of its apparently anomalous properties. The resistance of the ester group to saponification and of the ring E double bond to hydrogenation are characteristic of VIII, whereas the presumed molecular compound obtained earlier by reaction of alstonine with dinitrophenylhydrazine (54) is probably a derivative of its open-chain carbonyl equivalent (XI) (55). 

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