Quinine compounds

Bitter Substances. Quinine compounds are rejected at very... 

Supplement (combined with Volumes XXIV and 1936 3458-3793 methane, 25. Pyrimidine, 89. Pyrazine, 91. Nicotine, 110. Dipyridyl, 199. Phenanthroline, 227. Hydroxy compounds, 348 Cinchonine, 424. Quinine, 511. Indigo white, i... 

Description of Method. Quinine is an alkaloid used in treating malaria (it also is found in tonic water). It is a strongly fluorescent compound in dilute solutions of H2SO4 (f = 0.55). The excitation spectrum of quinine shows two absorption bands at 250 nm and 350 nm, and the emission spectrum shows a single emission band at 450 nm. Quinine is rapidly excreted from the body in urine and is easily determined by fluorescence following its extraction from the urine sample. 

A persistent idea is that there is a very small number of flavor quaUties or characteristics, called primaries, each detected by a different kind of receptor site in the sensory organ. It is thought that each of these primary sites can be excited independently but that some chemicals can react with more than one site producing the perception of several flavor quaUties simultaneously (12). Sweet, sour, salty, bitter, and umami quaUties are generally accepted as five of the primaries for taste sucrose, hydrochloric acid, sodium chloride, quinine, and glutamate, respectively, are compounds that have these primary tastes. Sucrose is only sweet, quinine is only bitter, etc saccharin, however, is slightly bitter as well as sweet and its Stevens law exponent is 0.8, between that for purely sweet (1.5) and purely bitter (0.6) compounds (34). There is evidence that all compounds with the same primary taste characteristic have the same psychophysical exponent even though they may have different threshold values (24). The flavor of a complex food can be described as a combination of a smaller number of flavor primaries, each with an associated intensity. A flavor may be described as a vector in which the primaries make up the coordinates of the flavor space. 

Replacing one carbon atom of naphthalene with an a2omethene linkage creates the isomeric heterocycles 1- and 2-a2anaphthalene. Better known by their trivial names quinoline [91-22-5] (1) and isoquinoline [119-65-3] (2), these compounds have been the subject of extensive investigation since their extraction from coal tar in the nineteenth century. The variety of studies cover fields as diverse as molecular orbital theory and corrosion prevention. There is also a vast patent Hterature. The best assurance of continuing interest is the frequency with which quinoline and isoquinoline stmctures occur in alkaloids (qv) and pharmaceuticals (qv), for example, quinine [130-95-0] and morphine [57-27-2] (see Alkaloids). 

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

Like other alkaloids of this group, quinine forms molecular compounds with a variety of organic substances. With benzene and toluene it produces compounds of the formulae B. CgHg and B. C,Hg respectively, with phenol it gives the crystalline product B. CgHjOH, and similar combinations with polyhydric phenols, ethers, aldehydes and ketones are known. One of the most characteristic of these substances is cupreine-quinine, a combination of the two alkaloids, obtainable from cuprea bark, and at first regarded as a new alkaloid, and named homoquinine. ... 

Numerous new salts and additive compounds of cinchona alkaloids, and especially of quinine, have been described, of which only a few can be mentioned as examples quinine additive compounds with sulph-anilamide, t quinine salts of (+) and (—)-pantothenic acid, °( > quinine sulphamate and disulphamate, °( organo-mercury compounds of quinine and cinchonine such as quinine-monomercuric chloride. Various salts and combinations of quinine have also been protected by patent, e.g., ascorbates and nicotinates. 

In the ease of the dextrorotatory pair, einchonine and quinidine, these hydroxydihydro-bases may lose a molecule of water between the two. CHOH. groups at positions 9 and 10 with the formation of ether oxides, represented by formula (C) of which there should be a pair of stereoiso-merides for eaeh alkaloid. This type of compound has not been obtained from the laevorotatory bases, einchonidine and quinine. 

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-... 

How richly this prophecy has come true is read in the scientific literature of organic chemistry. His first major success was the synthesis of quinine, a problem he began worrying as a high school student. This compound was to be typical of the difficult molecules he has successfully... 

Many racemic mixtures can be separated by ordinary reverse phase columns by adding a suitable chiral reagent to the mobile phase. If the material is adsorbed strongly on the stationary phase then selectivity will reside in the stationary phase, if the reagent is predominantly in the mobile phase then the chiral selectivity will remain in the mobile phase. Examples of some suitable additives are camphor sulphonic acid (10) and quinine (11). Chiral selectivity can also be achieved by bonding chirally selective compounds to silica in much the same way as a reverse phase. A example of this type of chiral stationary phase is afforded by the cyclodextrins. 

Note Tertiary amines and quaternary ammonium compounds yield stronger colors than primary amines [25]. The dipping solution can also be used as spray solution [44]. Other reagent compositions have also been reported in the literature (1, 3, 6, 12, 13, 15, 18, 21, 23, 41] In some cases the reagents have been made up in acetone [38, 39], methanol [14] or ethanol [37] and/or acidified with hydrochloric acid [3, 33, 37-40]. The concentrations of hexachloroplatinic(IV) acid have been in the range of 0.05 -0.4 those of potassium iodide between 0.5 and 24spray solution containing 2% potassium iodide and 0.23170 hexachloroplatinic(IV) acid hexahydrate in N-hydro-chloric acid is reported to yield the best coloration results with respect to detection sensitivity and color differentiation in the detection of morphine, codeine, quinine, methadone and cocaine [46]. Acidic reagent solutions have been recommended for benzodiazepines [10, 11]. Sulfones do not react [39]. 

Reduction of the isoprenyl groups of isohumulone and p-isohumulone to tetrahydro- and hexahydro-isohumulone, respectively, increases the lipophilicity of the resultant products. A corresponding increase in their bitterness was observed. A similar increase in bitterness was reported for hydroquinine following reduction of the vinylic double bond of quinine (117). Because the stereochemistry of the quinines does not have any significant effect on the bitterness, this change must be due to change in the relative lipophilicity of the compound. 

Fig. 2.43 Compounds 166-169, quinine relatives from Cinchona. Compound 170, a generalized sugar ester from Lycopersicon pennellii...

Sulfoxides without amino or carboxyl groups have also been resolved. Compound 3 was separated into enantiomers via salt formation between the phosphonic acid group and quinine . Separation of these diastereomeric salts was achieved by fractional crystallization from acetone. Upon passage through an acidic ion exchange column, each salt was converted to the free acid 3. Finally, the tetra-ammonium salt of each enantiomer of 3 was methylated with methyl iodide to give sulfoxide 4. The levorotatory enantiomer was shown to be completely optically pure by the use of chiral shift reagents and by comparison with a sample prepared by stereospecific synthesis (see Section II.B.l). The dextrorotatory enantiomer was found to be 70% optically pure. 

It is difficult to prove that quaternary ammonium compounds can cross lipid bilayers using cell uptake experiments, since several mechanisms may be operative, and separating contributions from each may be very difficult [1]. It may be an advantage to use PAMPA to investigate transport properties of permanently ionized molecules. Of all the molecules whose permeabilities were measured under iso-pH conditions in 2% DOPC/dodecane, verapamil, propranolol, and especially quinine seem to partially violate the pH partition hypothesis, as shown in Figs. 7.47a-c. In Fig. 7.47c, the solid line with slope of +1 indicates the expected effective permeability if the pH partition hypothesis were strictly adhered to. As can be seen at pH 4... 

At the time, little was known about the internal structure of compounds or about how one compound was transformed into another. Chemists concentrated instead on the proportions of various chemicals in a substance. Hofmann realized that the proportions of ingredients in the antimalaria drug quinine— 20 equivalents of carbon, 11 equivalents of hydrogen, 1 equivalent of nitrogen, and 2 equivalents of oxygen —were almost identical to those in aniline. The difference was only two equivalents of water. Hofmann speculated that he might be able to turn aniline into quinine. With European colonization headed toward the tropics, the drug was desperately needed. 

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