A. Quinine
Biological Sources It is obtained from the bark of Cinchona calisaya Wedd; Cinchona ledgeriana Moens ex Trimen; Cinchona officinalis Linn. f.; Cinchona robusta How; and Cinchona succirubra Pavon ex Klotzsch belonging to family Rubiaceae.
Chemical Structure
(8α, 9R)-6’-Methoxycinchonan-9-ol, (C20H24N2O2).
Isolation The schematic method of isolation of the Cinchona Alkaloids in general and that of quinine in particular has been provided in the following Flow-chart in a sequential manner. Hence, this particular flow-chart also includes the method of isolation of other important members of this group i.e., quinidine, cinchonine and cinchonidine as given under.
Notes
1. Bisulphates of cinchona as alkaloids [B.H2SO4] are readily soluble in water.
2. Quinine sulphate [Br.H2SO4] is sparingly soluble in water [1:720].
3. Cinchonine is practically insoluble in ether.
4. Tartrates of Quinine and Cinchonidine are insoluble, whereas the tartrates of Cinchonine and Quinidine are soluble in water.
Characteristic Features
1. The orthorhombic needles obtained from absolute ethanol are triboluminescent and having mp 177°C (with some decomposition).
2. It sublimes in high vacuum at 170-180°C.
3. Its specific rotation is [α ]D15 -169o (C = 2 in 97% ethanol); α ]D17 -117o (C = 1.5 in chloroform); and [α ]D15 -285o (C = 0.4 M in 0.1 N H2SO4).
4. Its dissociation constant pK1 (18°) is 5.07 and pK2 9.7.
5. Neutral Salt of Quinine [(B)2.H2SO4.8H2O]: It is formed by neutralization from boiling water, which is sparingly soluble in water (viz., 1 in 720 at 25°C). The octahydrate neutral salts of quinine undergoes efflorescence on being exposed to air and gets converted to the corresponding dihydrate salt which is more stable.
6. Acid Sulphate of Quinine [(B).H2SO4.7H2O]: The quinine bisulphate is soluble in water (1 in 8.5 at 25°C) and in ethanol (1 in 18). The aqueous solution is acidic to litmus.
7. Tetrasulphate Salt of Quinine [(B)2.2H2SO4.7H2O]: The tetrasulphate salt of quinine is very soluble in water.
Identification Tests
1. Fluorescence Test: Quinine gives a distinct and strong blue fluorescence when treated with an oxygenated acid, such as: acetic acid, sulphuric acid. This test is very marked and pronounced even to a few mg concentration of quinine.
Note: The hydrochloride and hydroiodide salts of quinine do not respond to this fluorescence test.
2. Thalleioquin Test: Add to 2-3 ml of a weakly acidic solution of a quinine salt a few drops of bromine-water followed by 0.5 ml of strong ammonia solution, a distinct and characteristic emerald green colour is produced. The coloured product is termed as thalleioquin, the chemical composition of which is yet to be established. This test is so sensitive that quinine may be detected to a concentration as low as 0.005%.
Notes: Quinidine and cupreine (a Remijia alkaloid) give also a positive response to this test; but cinchoninine and cinchonidine give a negative test.
3. Erythroquinine Test (or Rosequin Test): Add to a solution of quinine in dilute acetic acid 1-2 drops of bromine water, a drop of a solution of potassium ferrocyanide [K4(FeCN)6] (10% w/v), and to it add a drop of strong ammonia solution, the solution turns red instantly. In case, it is shaken immediately with 1 ml of chloroform, the red colour is taken up by the chloroform layer.
4. Herpathite Test: To a boiling mixture containing 0.25 g of quinine in 7.5 ml glacial acetic acid, 3 ml ethanol (90% v/v), 5 drops of conc. sulphuric acid and add to it 3.5 ml of 1% iodine solution in ethanol, the appearance of crystals of iodosulphate of quinine (i.e., sulphate of iodo-quinine)-is known as Herpathite after the name of its discoverer. It has the chemical composition [(B4).3H2SO4.2HI.I4.3H2O] which separates out as crystals (on cooling), having a metallic lustre that appears dark green in reflected light and olive green in transmitted light.
Uses
1. It is used as a flavour in carbonated beverages.
2. It is widely used as an antimalarial agent in tropical countries.
3. It is employed as a skeletal muscle relaxant.
Biosynthesis of Quinine The various steps whereby Coryanthe-type indole alkaloids are converted to quinoline derivatives have not yet been elucidated and hence established. Therefore, only a partial biosynthetic pathway may be written for quinine as given under.
