CINCHONA BARK, ALKALOIDS OF. About 3o dis tinct alkaloids have been isolated from cinchona bark, of which quinine is by far the most important, followed by quinidine, cinchonidine and cinchonine. Owing to the therapeutical im portance of cinchona bark and its four principal alkaloids most of the National Pharmacopeias prescribe methods of estimating these constituents in the bark and lay down standards both for the bark and for quinine. Thus the British Pharmacopeia re quires that red cinchona bark should yield from 5% to 6% of alkaloids, of which not less than half must consist of quinine and cinchonidine, and for quinine sulphate a test is prescribed which excludes all but a minimum quantity of cinchona alkaloids, other than quinine. (For further information see ALKALOIDS.) Quinine, C20H2402N2.—This alkaloid is rarely seen or used, except in the form of its salts with acids. Though it contains two atoms of nitrogen it behaves as a monoacidic base yielding a sulphate of the formula (C2oH2402N2)2, popularly known as "quinine." It crystallizes in bulky masses of colourless, glistening needles, which become dull on exposure to air owing to the loss of five of their molecules of water of crystallization, so that the thoroughly, stable, air-dry salt has the composition (C20H2402N2)2, H2SO4, 2H20. It is sparingly soluble in water, more so in alcohol and still more in a mixture of alcohol and chloroform. The solutions are laevorotatory and those in water, especially when acidified, are strongly fluorescent. Two other sulphates, C20H2402N2i (so-called disulphate) and (so-called tetra-sulphate) are known and are used when more soluble salts are required. Quinine hydrochloride HC1, which closely resembles the ordinary sulphate in appearance but has the advantage of being a little more soluble in water, is also in use. In addition, a great variety of special salts have been made in attempts to com bine the therapeutic advantages of quinine with those of medic inally valuable acids, e.g., quinine salicylate, acetylsalicylate, valerianate, cacodylate, etc.
On reduction quinine furnishes hydroquinine, which also oc curs in cinchona bark and is the raw material for the production of a series of drugs in which the side-chains of quinine are modi fied to enhance its therapeutic properties in certain directions. The best known of these modified cinchona alkaloids is "eucupin." Quinidine, C20H2402N2 (also called conquinine). This alkaloid, which is a dextrorotatory isomeride of quinine, crystallizes from alcohol in colourless prisms and melts when dry at 171.5°C. It forms two series of salts analogous with those of quinine.
Cinchonine C19H220 N2.-This alkaloid crystallizes from al cohol in rhombic prisms and melts at 264°C. It is dextrorotatory in solution and like the other cinchona alkaloids yields two series of salts with acids.
Cinchonidine, C19H220 N2.-This laevorotatory isomeride of cinchonine (see above), is one of the chief constituents of the mixture of alkaloids present in red cinchona bark, the variety now generally produced for making galenical preparations of cin chona. It crystallizes from alcohol in large colourless prisms, melting at 207°C, and corresponds with quinine in being laevo rotatory in solution, but is unlike it in showing no fluorescence in dilute sulphuric acid. It forms two series of salts, analogous with those of quinine described above.
These four cinchona alkaloids have been the subject of inves tigations designed to determine their constitution and permit of their synthesis, almost continuously since they were discovered in 1820. The reactions of the four alkaloids indicate that they can all be represented by the following general formula due to Rabe (1909) and based on that of (1906), which repre sents them as containing a quinoline (left) and a quinuclidine (right) nucleus, joined by a secondary alcohol group. The chemi cal differences between the two pairs (1) quinine and quinidine and (2) cinchonidine and cinchonine, depend on the fact that in the first pair R is the group and in the second pair R is a hydrogen atom. In all four alkaloids R' is the group CH : CH2 which can either be oxidized to a carboxyl group .COOH, giving rise to a new alkaloid from each of the four, or can be reduced to giving rise also to four new alkaloids (hydro-quinine, hydro-cinchonine, etc.). These eight new alkaloids can in turn each produce series of new derivatives, some of which are of special interest since in them the therapeutic properties of the parent alkaloids seem to be enhanced at least in certain directions.
Further it should be noted that there is now some reason to be lieve that the protozooicidal action of these alkaloids, to which is due their value in malaria, is associated mainly with the quinoline nucleus, whilst their action on the heart, which has led to the use of quinidine in cardiac therapeutics, is due to the quinuclidine nucleus, since sparteine, which also contains this nucleus, is stated to exert a similar action. (See also QUININE.) (T. A. H.)