Reactions of the Alkaloids

We may turn now to a general consideration of the chemistry of the major cinchona alkaloids, in terms of the established structures, (XXV, R = H) for cinchonine and cinchonidine, and (XXV, R = OCH ) for quinine and quinidine. 

The major transformations undergone by the alkaloids devolve from the presence in the bases of the ethanolamine system (XXVI, Q — 4r quiuolyl or 6 methoxy-4-quinolyl). 

We shall direct attention first to the special properties conferred on the system by its attachment at the -position of a quinoline nucleus. Any 

XXVIIa XXYII6). Thus a hydrogen atom a to such a group rill be relatively easily removed by basic reagents, and the resulting anion may undergo the manifold reactions characteristic of such centers. These 

R OCHi). It may be noted that quinine and quinidine are converted to the same ketone, as are cinchonine and cinchonidine. 

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Constitution. When coniine is distilled with zinc dust or heated with silver acetate/ a new base, coiiyrine, CgH N, differing from coniine by six atoms of hydrogen, is formed. This on oxidation yields pyridine-2-carboxylic acid and, since it is not identical with 2-isopropylpyridine, must be 2-propylpyridine (I). When coniine is heated with hydriodic acid at 300° it yields w-octane (II). These and other observations due mainly to A. W. Hofmann, made it clear by 1885 that coniine was probably a-propylpiperidine (III), and this has been amply confirmed by other reactions of the alkaloid and by syntheses. Thus, Wolffenstein showed that on oxidation with hydrogen peroxide, coniine is converted into amino-w-propylvaleraldehyde (IV) ... 

The Freneh authors realised that in eertain respeets this symmetrical formula, with the two equivalent nitrogen atoms, was difficult to reconcile with certain of the properties and reactions of the alkaloid. ... 

From these and other experimental results Pinner and Schwarz suggested that pilocarpine could be represented by formula (V), and subsequently Jowett confirmed this by the preparation of a series of disubstituted glyoxalines from wopilocarpine by distillation with soda-lime, 1 although he pointed out that the reactions of the alkaloid were... 

A diprenylacridone (41) obtained from the roots of Atalantia monophylta33 has unfortunately been given the same name, i.e. atalaphyllidine, as a different acridone isolated previously from this species (see Vol. 7). The presence of two prenyl groups in the new alkaloid was indicated by the n.m.r. spectrum, by catalytic reduction to a tetrahydro-derivative, and by conversion into compound (42) when treated with formic acid. The reaction of the alkaloid with methyl iodide and potassium carbonate afforded the corresponding N-methyltrimethoxyacridone. 

Reactions of the alkaloids lythrine (15 R = H) and lythridine (17) have been studied (Scheme l).17 Mercuric-acetate-induced stereoselective addition to the unsaturated lactone group of lythrine (15 R = H) results in introduction of a methoxy-group at the benzylic / -position to give a product (16) that is epimeric at C-13 with the hydroxylated alkaloids, cf. (17). Benzylic substituents undergo ionization and trapping with solvent to give more stable epf-products cf (17) - (16). 

The determination of atropine/hyoscya-mine or scopolamine is based on the reaction of the alkaloid with p-dimethylaminobenzaldehyde reagent in concentrated H2SO. The intensity of the color so produced being measured in a photoelectric absorptiometer using a green filter. 

IV) thus deduced for the alkaloid has been confirmed by the degradation of the dihydroxytrimethoxyquinoline to 2 4 5-trimethoxybenzoic acid, and a number of other reactions of the alkaloid have been described (26). 

Azafluoranthene bases have been found to date only within the family Menisper-maceae. A recent addition to this small group of optically inactive alkaloids is norrufescine, C18H15NO4, whose PMR spectrum is close to that of the known base rufescine. Diazomethane 0-methylation of norrufescine generated rufescine. The location of the phenolic function in ring D was confirmed by a positive coupling reaction of the alkaloid with /7-nitrobenzenediazonium chloride. ... 

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