Quinine alkaloids Cinchona Bark

A number of naturally occurring pharmacologically active alkaloids possess quinoline and isoquinoline skeleton. For examples, papaverine from Papa-ver somniferum is an isoquinoline alkaloid and quinine from Cinchona barks is a quinoline alkaloid that has antimalarial properties. 

Leaching or solid-liquid extraction are terms that describe the extraction of soluble constituents from a solid or semisolid by means of suitable solvents. The process, which is used whenever tea or coffee is made, is an important stage in the production of many fine chemicals found naturally in animal and vegetable tissue. Examples are found in the extraction of fixed oils from seeds, in the preparation of alkaloids, such as strychnine from Nux vomica beans or quinine from Cinchona bark and in the isolation of enzymes, such as rennin, and hormones, such as insulin, from animal sources. In the past, a wider importance attended the process because the products of simple extraction procedures, known as galenicals, formed the major part of the ingredients used to fulfill a doctor s prescription. 

Quinidine. Formula see quinine. C20H24N2O2, Mr 324.42, [a]o +230° (CHCI3) a typical Cinchona alkaloid, the dextrorotatory diastereomer of quinine from cinchona bark. Crystal plates, poorly soluble in water, better soluble in alcohol, ether, chloroform, mp. 175 °C, obtained from the mother liquor from the isolation of quinine and purified by formation of salts and precipitation. It is also obtained in yields of over 40% semisynthetically from quinine. 

The importance of heterocycles in life was recognized as the nascent stage of organic chemistry two centuries ago with isolation of alkaloids such as morphine from poppy seeds, quinine from cinchona barks, and camptothecin from the Chinese joy tree. Today, heterocycles are found in numerous fields of biochemical and physiological such as photosynthesis, amino acids, DNA bases, vitamins, endogenous neurotransmitters, and so on. 

QuinidJne. Quinidine, an alkaloid obtained from cinchona bark (Sinchona sp.), is the dextrorotatory stereoisomer of quinine [130-95-0] (see Alkaloids). The first use of quinidine for the treatment of atrial fibrillation was reported in 1918 (12). The sulfate, gluconate, and polygalacturonate salts are used in clinical practice. The dmg is given mainly by the oral (po) route, rarely by the intravenous (iv) route of adniinistration. It is the most frequentiy prescribed po antiarrhythmic agent in the United States. The clinical uses of quinidine include suppression of atrial and ventricular extrasystoles and serious ventricular arrhythmias (1 3). 

Analyses of Cinchona Barks. For galenical preparations, pharmacopoeia recognition is usually restricted to barks of cultivated cinchona species known to yield total alkaloids satisfactory in composition thus, the British Pharmacopoeia 1932 prescribes the varieties to be used, and specifies not less than 6 per cent, of total alkaloids, of which at least half must be quinine and cinchonidine, determined by the process prescribed. Numerous other processes have been published and references to the more important of these are given under the following headings —identifica-... 

The oldest effective drug for the treatment of this disease is indisputably quinine. Although the antipyretic activity of cinchona bark was known to the Incas, it remained for the Jesuit missionaries to uncover its antimalarial properties in the early seventeenth century. The advance of organic chemistry led to the isolation and identification of the alkaloid, quinine, as the active compound at the turn of this century. The emerging clinical importance of this drug led up to the establishment of cinchona plantations in the Dutch East Indies. This very circum-... 

Cinchona alkaloids [Qninidine (6), Quinine (7)] Cinchona spp. (Cinchona bark) Cardiac antiarrhythmic Antimalarial... 

Quinine is a natural alkaloid obtained from cinchona bark. 

Cinchona and its alkaloids, particularly quinine, have been used for many years in the treatment of malaria, a disease caused by protozoa, of which the most troublesome is Plasmodium falciparum. The beneficial effects of cinchona bark were first discovered in South America in the 1630s, and the bark was then brought to Europe by Jesuit missionaries. Religious intolerance initially restricted its universal acceptance, despite the widespread occurrence of malaria in Europe and elsewhere. The name cinchona is a mis-spelling derived from Chinchon. In an often quoted tale, now historically disproved, the Spanish Countess of Chinchon, wife of the viceroy of Peru, was reputedly cured of malaria by the bark. For... 

Quinine sulfate, the classic drug, the salt of an alkaloid obtained from cinchona bark, has been superseded by newer drugs in most parts of the world. It is only a fairly good suppressant, even in toxic dosage, and is so rapidly eliminated that it must be given at very frequent intervals to maintain its effects. When used to check an established attack, it achieves the control of parasitemia in 96 h that chloroquine accomplishes in little more than 72 h, and its effects on fever and most other symptoms also lag (Figure 22.3). 

Quinine is a naturally occurring alkaloid obtained from Cinchona bark, with a mechanism of action similar to that of chloroquine. Quinine is very useful in treating chloroquine-resistant Plasmodium falciparum. In toxic doses, it may cause cinchonism characterized by tinnitus, headache, nausea, and visual disturbances. 

Quinine (14a), cinchonine (14b), quinidine (15a), and cinchonidine (15b), which are so-called cinchona alkaloids, occur in cinchona barks. Although 14a and 15a are the diastereomers of each other, they have been used as alternatives of the corresponding enantiomers, respectively. Quininium and quinidinium ions (14a H+ and 15a H+) have two possible hydrogen-bond donors, a ternary ammonium ion and a hydroxy group. They also have two... 

Quinine (C2oH24N202) is the most important alkaloid derived from cinchona bark. It is used as an antimalarial drug. For quinine pK = 5.1 and pKb2 = 9.7 (pKb = —log Kb). One gram of quinine will dissolve in 1900.0 mL of water. Calculate the pH of a saturated aqueous solution of quinine. Consider only the reaction Q +- H20. QH+ +- OH- described by pKb] where Q = quinine. 

Quinidine. Derived from cinchona bark (minor alkaloid), the anti-malarial agent quinine being a major alkaloid... 

The cinchona tree, from the bark of which these alkaloids are obtained, was originally found only on the eastern slope of the Andes in South America. The cultivation of this species, and other species of the same genus, was introduced into Java, India, Ceylon, Jamaica and Australia. At present the production of bark in Java is greater than in any other country. As early as 1639 the cinchona bark was introduced into Europe but it was not until 1792 that an impure alkaloid was isolated and a little later given the name quina. In 1820 this impure alkaloid was separated into two compounds named quinine and cinchonine. The bark contains about 3 per cent quinine combined with acids, tannic and quinic, from which it is set free by the action of lime. The free base is then extracted with petroleum ether or... 

Derivation Finely ground cinchona bark mixed with lime is extracted with hot, high-boiling paraffin oil. The solution is filtered, shaken with dilute sulfuric acid, and the latter neutralized while still hot with sodium carbonate on cooling, quinine sulfate crystallizes out. The sulfate is then treated with ammonia, the alkaloid being obtained. 

QUINIDINE Quinidine is one of the quinoline alkaloids in Cinchona bark. (See POl, Antimalaria-drugs). Thus, quinidine is an antiarrythmic drug, whereas its stereoisomer, quinine, is an antimalarial. In antiarryth-mically effective doses quinidine reduces the contraction capacity of the heart. The minute volume of the heart diminishes through its negative inotropic effect. Quinidine is used clinically for treatment of relapse into auricle fibrillation, and at extrasystohcs and paroxysmal tachycardia and ventricular tachycardia. 

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