Dextrorotatory stereoisomers

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). 

Dextromethorphan is the dextrorotatory stereoisomer of a methylated derivative of levorphanol. It is purported to be free of addictive properties and produces less constipation than codeine. The usual antitussive dose is 15-30 mg three or four times daily. It is available in many over-the-counter products. Dextromethorphan has also been found to enhance the analgesic action of morphine and presumably other -receptor agonists. However, abuse of its purified (powdered) form has been reported to lead to serious adverse events including death. 

Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified from the bark in 1820, and it has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1-3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. The pharmacokinetics of quinine varies among populations. Individuals with malaria develop higher plasma levels of the drug than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine. 

Dextrorotatory stereoisomer that reflects plane-polarized hght to the right. 

A dextrorotatory stereoisomer of quinine, obtained from the bark of species of Cinchona (Rubiaceae). Commercial samples may contain 20 to 30% of hydroquinidine. 

Dextromethorphan, an effective antitussive drug, is the dextrorotatory stereoisomer of a derivative of levorphanol. The drug is available without a prescription and is the active component in many over-the-counter cough suppressants. Dextromethorphan has no appreciable analgesic activity and minimal abuse liability. In comparison with codeine—also an effective antitussive—dextromethorphan causes less constipation. The answer is (D). 

Clinical use The main use of quinine is in P falciparum infections resistant to chloroquine. Quinine is sometimes used with doxycycline to shorten the duration of therapy and limit toxicity. Quinidine, the dextrorotatory stereoisomer of quinine, is used intravenously in the USA for treatment of severe falciparum malaria. To delay emergence of resistance, the drugs should not be used routinely for prophylaxis. 

With chiral molecules, if the reflection of one of them in a mirror was viewed, the reflection would show the other stereoisomer. These stereoisomers are called mirror images or enantiomers. Enantiomers are optically active one rotates the plane of polarized light to the right (clockwise) and is called the dextrorotatory stereoisomer, whilst the other rotates the plane of polarized light to the left (anticlockwise) to the same extent and is called the laevorotatory stereoisomer. A mixture of each... 

The separation of a racemic mixture into its enantiomeric components is termed resolution The first resolution that of tartaric acid was carried out by Louis Pasteur m 1848 Tartaric acid IS a byproduct of wine making and is almost always found as its dextrorotatory 2R 3R stereoisomer shown here m a perspective drawing and m a Fischer projection... 

Chirality is an important aspect of aroma chemicals since enantiomers of the same compound may possess different organoleptic characters. Chirality means the occurrence of one or more asymmetric carbon atoms in an organic molecule. Such molecules exhibit optical activity and therefore have the ability to rotate plane-polarised light by equal amounts but in opposite directions. In other words, two stereoisomers which are mirror images of each other are said to be enantiomers. If two enantiomers exist in equal proportions, then the compound is called racemic. Enantiomers can be laevorotatory (, I, -, S), meaning rotating the plane of the polarised light to the left or dextrorotatory (°, d, -f, R), that is. 

RGURE 1 Pasteur separated crystals of two stereoisomers of tartaric acid and showed that solutions of the separated forms rotated polarized light to the same extent but in opposite directions. These dextrorotatory and levorotatory forms were later shown to be the (R,R) and (S,S) isomers represented here. The RS system of nomenclature is explained in the text. 

Biotin contains three chiral centers and therefore has eight stereoisomers.1819 Of these, only one, the dextrorotatory (-i-)-biotin, is biologically active.19 20 The vitamin is readily oxidized to die sulfoxide and sul-fone. The sulfoxide can be reduced back to biotin by a molybdenum-containing reductase in some bacteria (see also Chapter 16, Section H).20a Biotin is synthesized from pimeloyl-CoA (see chapter banner, p. 719 and Eq. 24-39). Four enzymes are required. Two of them, a... 

The single most important physical property that differentiates enantiomers is their ability to rotate the plane of plane polarized light. This property is called optical activity and is displayed only by chiral molecules. Thus, stereoisomers which are also chiral are known as optical isomers. Chiral molecules that rotate polarized light in a clockwise fashion are termed dextrorotatory (d) while those that rotate the beam counterclockwise are levorotatory (/). Enantiomers have optical rotations of die same magnitude but of different signs (d or /). 

Each stereoisomer in a pair of enantiomers has the property of being able to rotate monochromatic plane-polarized light. The instrument chemists use to demonstrate this property is called a polarimeter (see your text for a further description of the instrument). A pure solution of a single one of the enantiomers (referred to as an optical isomer) can rotate the light in either a clockwise (dextrorotatory, +) or a counterclockwise (levorotatory, -) direction. Thus those molecules that are optically active possess a handedness or chirality. Achiral molecules are optically inactive and do not rotate the light. 

The structural formula (Figure 9-23) contains three asymmetric carbon atoms, and eight different stereoisomers are possible. Only the dextrorotatory D-biotin occurs in nature and has biological activity. Biotin occurs in some products in free form (vegetables, milk, and fruits) and in other products is bound to protein (organ meats, seeds, and yeast). Good sources of the vitamin are meat, liver, kidney, milk, egg yolk, yeast, vegetables, and mushrooms (Table 9-27). 

When a molecule contains only one chiral center, the two stereoisomers are known as enantiomers. These may be referred to or labeled using the configurational descriptors as either R rectus meaning righthanded) or S (sinister meaning left handed), or alternatively, D (dextrorotatory) or l (levorotatory). The D and l configurational descriptors are... 

Diastereomers are stereoisomers that are not mirror images of each other. Diastereomers have different physical properties. And they maybe dextrorotatory, levorotatory or inactive. 

Biotin contains three chiral centers and therefore has eight stereoisomers. Of fhese, only one, fhe dextrorotatory (+)-biotin, is biologically active. ... 

The natural ketone 20 was dextrorotatory in hexane, and (35,115)-20 as well as (35,1 li )-20 showed positive rotations, while (31 ,111 )- and (31 ,115)-20 were levorotatory. The natural 20 must therefore be either (35,115)-or (35,1 ll )-20. As chloroform solutions, all the stereoisomers of 20 showed IR spectra that were identical to... 

Each member of a pair of stereoisomers will rotate plane-polarized light in different directions. A polarimeter is used to measure the direction of rotation of plane-polarized light. Compounds that rotate light in a clockwise direction are termed dextrorotatory and are designated by a plus sign (+). Compounds that rotate light in a counterclockwise direction are called levorotatory and are indicated by a minus sign (—). 

Organoleptic Properties. Stereochemical differences of enantiomeric excipients may influence perception by sensory organs. Kutti [17] reported as early as 1886 that the interaction of stereoisomer with chiral receptors led to chiral discrimination as a consequence of the formation of diastereomers. He observed that the dextrorotatory asparagine has a sweet taste whereas the levorotatory form is tasteless. Greenstein and Winitz [18] and Solms et al. [19] reported such differences for many amino acids. Shallenberger et al. [20] reported that for some monosaccharides, both isomers have similar sweetness. In contrast, aspartame (A-aspartylalanine methyl ester) is marketed as the l,l isomer because it is more than 100 times as sweet as sucrose. However, the l,d diastereomer of aspartame is bitter [11], It should be noted that the individual differences of perception of these properties could vary. 

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