R- -Carvone

Enantiomers can have striking differences however m properties that depend on the arrangement of atoms m space Take for example the enantiomeric forms of carvone (R) (—) Carvone is the principal component of spearmint oil Its enantiomer (5) (+) carvone is the principal component of caraway seed oil The two enantiomers do not smell the same each has its own characteristic odor... 

Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

Picrotoxin, a potent antagonist of 7-aminobutyric acid at neural synapses, has been synthesized from (R)-(-) carvone as SM-goal (Sections 3.1 and 6.5). 

Figure 10. The CMS-Xa predictions for cross-section, the anisotropy parameter —P/2), and the chiral parameter in the carbonyl C li photoionization of (R)-carvone (I) and its indicated derivatives.

Bioassay of alternate molecular forms supports the view that the ORs are capable of resolving isomeric distinctions in neutral (non-biological) odourants. Stereochemical pairs of odours were tested for differential sensitivities in the blind subterranean mole rat (Spalax ehrenbergi). The subjects responded to one enantiomer, but not to its stereoisomer. Both sexes were attracted to the odour of R-(-)-carvone but unresponsive to S-(+)-carvone in contrast, males and females were repelled by the odour of (+)-citronellol, but not by (-)-citronellol (Heth et al., 1992). The lack of responsiveness by mole rats could be central due to lack of salience, or peripheral due to hyposmia/anosmia for one isomer. Both carvones have distinct odours for the human nose. 

At the cellular level, the various types of receptor, transporter, enzyme and ion charmel are all chiral in form. Thus although the enantiomers of a drug may have identical physicochemical properties, the way in which they may interact with chiral targets at the level of the cell will give rise to different pharmacod)mamic and pharmacokinetic properties. A few simple examples will illustrate how taste and olfactory receptors can differentiate between enantiomers. Thus R-carvone tastes like spearmint whereas the S-isomer tastes like caraway. Similarly, R-limolene smells like lemon whereas the S-enantiomer tastes of orange. 

A 500-mL, three-necked, round-bottomed flask is equipped with a 25-mL pressure-equalizing dropping funnel, a mechanical stirrer, and a Claisen adapter fitted with a nitrogen inlet adapter and a low temperature thermometer (Note 1). The flask is charged with 11.5 g (0.077 mol) of (R)-(-)-carvone (Note 2), 10.8 g (0.079 mol) of 1-methyl-l-(trimethylsilyl )allene (Note 3), and 180 mL of dry dichloromethane (Note 4), and then cooled below -75°C with a dry ice-acetone bath while a solution of 17.4 g (0.092 mol) of titanium tetrachloride (Note 5) in 10 ml of dichloromethane is added dropwise over 1 hr. After 30 min, the cold bath is removed, and the reaction mixture, which appears as a red suspension, is allowed to warm to 0°C over approximately 30 min. The resulting dark red solution is poured slowly into a 2-L Erlenmeyer flask containing a magnetically-stirred mixture of 400 mL of diethyl ether and 400 mL of water (Note 6). The aqueous phase is separated and extracted with... 

R)-(-)-Carvone was purchased from Aldrich Chemical Company, Inc. and distilled before use. 

FIGURE 1-23 Stereoisomers distinguishable by smell and taste in humans, (a) Two stereoisomers of carvone R) carvone (isolated from spearmint oil) has the characteristic fragrance of spearmint (S)-carvone (from caraway seed oil) smells like caraway, (b) Aspartame, the artificial sweetener sold under the trade name NutraSweet, is easily distinguishable by taste receptors from its bitter-tasting stereoisomer, although the two differ only in the configuration at one of the two chiral carbon atoms. 

Carvone (94) occurs as (+)-carvone, (-)-carvone or racemic carvone. (S)-(+)-Carvone is the main component of caraway oil (ca 60%) and dill oil and has a herbaceous odour reminiscent of caraway and dill seeds. (R)-(-)-Carvone occurs in spearmint oil at a concentration of 70-80% and has a herbaceous odour similar to spearmint [26]. (S)-(+)-Carvone (94) was used as substrate for bioconversions by selected microorganisms five... 

Scheme 28 Transformation of ( R)-carvone oxide into a fischerindole precursor...

Which of the following properties or methods can be used to distinguish between (R)-carvone and (S)-carvone ... 

R)-Carvone and (S)-carvone are enantiomers and can be distinguished from each other by their optical rotations, by circular dichroism and by smell. Laevorotatory (R)-carvone has a spearmint smell (spearmint = Mentha spicata), whilst (S)-(+)-carvone has a caraway odor. 

The same reaction carried out on R-( - )-carvone (1) affords a 3 1 mixture of two esters (equation I). 

Since initially neither the stereochemistry of the trisub-stituted double bond nor the absolute configuration of component XVI was known, we prepared all four of the possible geometric and optical isomers starting from either (J3)-(+)-carvone (Figure 6) or (R)-(-)-carvone, and only the 3Z,6R isomer was found to be attractive to the males (48). This is not a practical route to XVI a shorter synthesis of racemic XVI was subsequently published by Still and Mitra (51). 

Treatment of (R)-carvone with racemic lithiated 2b gave a mixture of the diastereomeric 1,2-adducts 80 at -78 °C and the diastereomeric cyclopropanes 81a,b, and the double addition product 82 as a single diastereoisomer at room temperature. The diastereoselectivity in the case of 81 was similar to that obtained when (5)-2b was employed. Compound 81 has been prepared as a single diastereoisomer by Corey and Chaykovsky.60... 

The reaction of racemic 147 with (R)-carvone, initially at -78 °C followed by warming to room temperature for 1 h, gave the vinylcyclopropane 151 in 72% yield and moderate diastereoselectivity (d.r. = 75 25). The stereochemistry of the major diastereoisomer shown in structure 151 from H NMR studies was that expected based on the stereochemical outcome of the reaction of racemic 147 with the achiral cyclic enones 146 and is consistent with our previously proposed chelated transition state90 for cyclic enones (compare with the transition state B). 

SYNS (-)-CARVONE 1-CARVONE (R)-CARVONE FEMA No. 2249 l-6,8(9)-p-MENTHADIEN-2-ONE (R)-(-)-p-MENTHA-6,8-DIEN-2-ONE l-l-METHYL-4-ISOPROPENYL-6-CYCLOHEXEN-2-ONE (R)-2-METHYL-5-(1-METHYLETHENYL)-2-CYCL0HEXEN-1-ONE (9CI)... 

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