Quinidine yields with chromic acid the same decomposition products as quinine.

Cinchonine, CHNO, the second most important alkaloid of these barks, when oxidized with potassium permanganate, yields cinchonic acid, which is a quinoline-carboxylic acid, CHN(COOH), cinchomeronic acid, which has just been stated to be a pyridine dicarboxylic acid, and a pyridine tricarboxylic acid. When cinchonine is treated with potassium hydrate, it is decomposed into quinoline and a solid body, which on further treatment yields a liquid base, CHN, which is probably lutidine. It has been found, moreover, that both tetrahydroquinoline and dihydroquinoline, hydrogen addition products of quinoline, are present. When cinchonine is distilled with solid potassium hydrate, it yields pyrrol and bases of both the pyridine and quinoline series.

Cinchonidine, when heated with potassium hydrate, yields quinoline also, and with nitric acid the same products as cinchonine.

Strychnine has been found to be a tertiary amine. When distilled with potassium hydrate, quinoline is formed.

Brucine is a tertiary diamine, that is, formed by substitution in a double ammonia molecule. When distilled with potassium hydrate it yields quinoline, lutidine, and two isomeric collidines.

The alkaloid atropine has been quite thoroughly studied with results of great interest. When heated with baryta-water or hydrochloric acid, it takes up a molecule of water and is split into tropine, CHNO, and tropic acid, CHO. This latter is phenyl-oxypropionic acid. Tropine, when heated to 180°C. with concentrated hydrochloric acid, splits off a molecule of water, and yields tropidine, CHN, a liquid base, with an odor resembling conine. When this tropidine is heated with an excess of bromine, it yields dibrompyridine.

Piperine, the alkaloid of pepper, has also been well studied. When boiled with alcoholic potash solution, it takes up a molecule of water and splits apart into piperic acid, CHO, and piperidine, CHN. This latter base has been shown to be a hydrogen addition product of pyridine, CHN. When heated with concentrated sulphuric acid, it is oxidized to pyridine. Piperidine hydrochlorate, also, when heated with excess of bromine to 180° C., yields dibrompyridine.

Sinapine, the alkaloid which exists as sulphocyanate in white mustard seed, yields, under the same reaction as that applied to atropine and piperine, quite different results. When boiled with baryta water, sinapine decomposes into sinapic acid, CHO, and choline, CHNO, the latter a well-known constituent of the bile, and produced also in the decomposition of the lecithin of the brain and yolk of egg.

Cocaine, the alkaloid of coca leaves, is decomposed by heating with hydrochloric acid into methyl alcohol, benzoic acid, and a crystalline base, ecgonine, CHNO.

Caffeine and theobromine have also quite different relations. Caffeine, it will be remembered, is the methyl ester of theobromine, and can be prepared from it. When caffeine is carefully oxidized with chlorine, it yields dimethyl-alloxan and methyl-urea. Both theobromine and caffeine are decomposed by heating to 240° C. in sealed tubes with hydrochloric acid, identical products being obtained. These products are carbon dioxide, formic acid, ammonia, methyl-amine, and sarcosine, the last three being of course in combination with the excess of hydrochloric acid. The artificial preparation of theobromine and caffeine from xanthine, and guanine also show clearly their relations.

If, having completed our survey of what has been done in the way of decomposing the alkaloids by the different classes of reagents, we review the field, it will be seen that with all the alkaloids mentioned, except the last four, a more or less immediate connection with the pyridine and quinoline bases has been indicated. The conviction accordingly forces itself upon us that, if we want to attack the problem of building up any of these important alkaloids artificially, we must turn to these bases as our starting point.

As already stated, both series occur in coal-tar and the pyridine series also more abundantly in bone-oil. Pyridine, picoline, lutidine, and collidine, the first four members of the pyridine series, have, moreover, all been formed synthetically, although the processes are not such as would yield the products as cheaply as they can be gotten from Dippel's oil. Quinoline, the first member of the higher series, had been made synthetically by several chemists, but by expensive and involved methods, when Skraup, in 1881, effected its synthesis from nitrobenzol and glycerin, or still better, a mixture of nitrobenzol and aniline with glycerin. This process allows of its being made on a commercial scale if desirable. Shortly after, by an application of the same principle, Dobner and Miller effected the synthesis of lepidine, the second member of the quinoline series.

At the same time that this general agreement to consider these bases as the starting point in the endeavor to effect the synthesis of the natural alkaloids had been arrived at by chemists, it was thought well to look into the question whether these bases and their immediate derivatives had any therapeutic value of their own.

Piperidine, the decomposition product of piperine, which we have shown may be considered to be hexahydropyridine, was examined by Dr. Kronecker, of Berlin, at the request of Prof. Hofmann, and was found to have an action upon animals in many respects resembling that of conine. Prof. Filehne, of Erlangen, who has studied a large number of these pyridine and quinoline derivatives, found, moreover, that the hydrochlorate of ethyl-piperidine had a physiological action quite analogous to that of conine.

The physiological action of quinoline itself has been studied quite extensively by Donath and others, and it was found that several of its salts were quite valuable febrifuges, acting very like quinine, and capable in cases of being used as a substitute for it. In general, the hydrogen addition products were found to be more active than the simple base, an observation entirely in accord with the theory formed by Wischnegradsky, and by Konigs, as the result of the study of the decomposition products of the alkaloids, viz., the alkaloids are in general hydrogen addition products of pyridine and quinoline, or of the two bases combined. Thus Prof. Filehne found that hydrochlorate of tetrahydroquinoline was much more energetic in its action than quinoline, but could not be used on account of a too powerful local effect. The hydrochlorate of dimethyl-tetrahydroquinoline, which was distinguished by its strong bitter taste, much resembling that of quinine, had an effect like that of curare poison. The most decided febrifuge action, however was found by Prof. Filehne to reside in the hydrochlorate of oxyhydro-methyl-quinoline, introduced to public notice by Prof. O. Fischer under the name of "Kairin," and in the acid sulphate of tetrahydro-methylquinoline, introduced under the name of "Kairolin." These compounds had a very surprising febrifuge action, without any unpleasant after effects or local disturbances.

The most active workers in the field of synthetic formation of the alkaloids have been Wischnegradsky, of St. Petersburg--who, unfortunately for science, died at an untimely age in 1880--Königs and Fischer, of Munich, and Ladenburg, of Kiel. The study of the decomposition products of the cinchona alkaloids especially points quite distinctly to the probable existence in quinine of a hydrogen addition product of pyridine, in combination with a methyl-quinoline group. The many experiments that are now being made to test this and other questions that suggest themselves, will not long leave us in the dark. Whether a practical commercial synthesis of quinine will follow is another matter, but it is within the bounds of possibility, or perhaps even of probability.

It must not be supposed that no syntheses of alkaloids have been effected as yet. By heating butyl-aldehyde with alcoholic ammonia is formed paraconine, an alkaloid isomeric with the natural conine, but differing in physiological action. By the action of sodium upon pyridine is produced a compound CHN, known as dipyridyl, and this, under the influence of nascent hydrogen, takes up six atoms and becomes isonicotine CHN, a physiologically active alkaloid, isomeric with the true nicotine. The formation of a series of alkaloids under the name of codeines, by the substitution of other organic radicals instead of methyl in the codeine reaction, has already been alluded to. Atropine can be formed by uniting tropine and tropic acid, the two decomposition products already noted. The latter of these products is already shown to be capable of synthetical formation, and the other will no doubt be formed in the same way. The artificial atropine is identical with the natural alkaloid. Ladenburg has also formed a series of artificial alkaloids, called tropeines, by uniting the base tropine with different organic acids, as in the case of the compound of mandelic acid and tropine, known as homatropine, an alkaloid of action similar to atropine, but possessing some decided advantages in its use.

Piperine has also been made by the uniting of piperidine and piperic acid, and, as piperidine has already been formed from pyridine, we have here a true synthesis also. Both theobromine and caffeine, its methyl derivative, have been made from xanthine, which itself can be formed from guanine, a constituent of guano.

We may conclude from this reference to what has been done in the last few years, that the reproach mentioned in first speaking of the alkaloids as a class, that almost nothing was known of their constitution, will not long remain, and that as their molecular structure is laid bare in these studies now being made, keen-sighted chemists will effect their artificial formation. When these most valuable compounds can be made by exact methods, in a state of entire purity, and at a cost much below that paid for the present extraction of them from relatively rare plants, organic chemistry will have placed all of us under obligations as great as those owing any branch of science, no matter how practical we call it.--Amer. Jour. of Pharmacy.