The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan.

  • Buttle, G. A. H. (Gladwin Albert Hurst), 1899-1983.
Date:
[1934]
Catalogue details

Licence: Public Domain Mark

Credit: The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan. Source: Wellcome Collection.

    19/22 (page 429)
    on its conversion into —CO— (quininone), —CH2— (desoxyquinine), :CH— (quinene) or —CH.OAc— (acetyldihydroquinine) [Giemsa and Oesteriin, 1933] and no change so far effected has left the activity unimpaired. Table B. Daily do3es r-■—A-\ Quantity Retardation Substance No. mg. days Ethylquitenine hydrochloride 6 5 5 /so-Amylquitenine dihydrochloride 6 5 6 The authors desire to place on record their indebtedness to Prof, van der Sleen of the Kina Bureau, Amsterdam, for information on a number of technical points connected with the analysis of cinchona alkaloids. They also owe thanks to Mr W. Solomon, B.Sc., for the preparation of the three cinchona alkaloid chlorides mentioned, to Messrs A. C. Camfield, E. M. Gibbs, and N. J. G. McLaren for much patient work on the fractionation and biological tests of the alkaloids, and to Messrs A. Bennett and H. C. Clarke for the micro-analyses. Chemical section. Crystallisable cinchona alkaloids. The impurities in commercial samples of the primary cinchona alkaloids are of two kinds. Each alkaloid contains its own reduction product, which in the case of quinidine is now shown to be present to the extent of 20 % and may be as high as 30 % [Dawson and Gar bade, 1930], while cinchonine usually contains about 14 % of dihydrocinchonine. These remarks apply to well-crystallised specimens of these alkaloids, usually accepted by chemists and biologists as pure owing to their constancy of melting- point and optical rotation. The amounts of dihydro-bases in quinine and cin- chonidine are much less but are not negligible. The other type of impurity is due to the difficulty of completely separating the components of each of the two similarly optically active pairs from each other, i.e. cinchonidine and quinine usually contaminate each other, as do quinidine and cinchonine, but com¬ ponents of the laevorotatory pair are not usually found in those of the dextro¬ rotatory pair and the converse is also true. The purification of any one of the four primary alkaloids thus involves two steps: (1) the removal of the second component of the similarly optically active pair, e.g. cinchonidine from quinine and vice versa, and (2) the elimination from each alkaloid of the dihydro-base, which naturally accompanies it. Much work has been expended in attempts to prepare each of the primary cinchona alkaloids in a pure state, but only two of the numerous papers on this subject need be referred to here [Tutin, 1909; Emde, 1932]. Tutin prepared pure quinine by repeated crystallisation of the acid sulphate, but was unable to prove that it was free from dihydroquinine. This proof is now supplied. Emde set out to prepare all eight alkaloids in a pure state, specially recommending for this purpose crystallisation of the dihydrobromides, but he did not prove the absence of the dihydro-bases from his final specimens of the four primary alkaloids. In the course of the present investigation, pure specimens of each of the primary alkaloids have been prepared, the chief criteria of purity adopted (apart from well-known specific tests, such as fluorescence, methoxyl determinations and the thalleioquin reaction) being (a) agreement of the ‘'found” and “calcu¬ lated” values for hydrogen absorbed, by the conversion of the vinyl group into Biochem. 1934 xxvm 28