S- -Limonene

Limonene S-limonene is responsible for the odor of lemon, and the iUlimonene for the odor of orange. 

In order to establish the correct absolute stereochemistry in cyclopentanoid 123 (Scheme 10.11), a chirality transfer strategy was employed with aldehyde 117, obtained from (S)-(-)-limonene (Scheme 10.11). A modified procedure for the conversion of (S)-(-)-limonene to cyclopentene 117 (58 % from limonene) was used [58], and aldehyde 117 was reduced with diisobutylaluminium hydride (DIBAL) (quant.) and alkylated to provide tributylstannane ether 118. This compound underwent a Still-Wittig rearrangement upon treatment with n-butyl lithium (n-BuLi) to yield 119 (75 %, two steps) [59]. The extent to which the chirality transfer was successful was deemed quantitative on the basis of conversion of alcohol 119 to its (+)-(9-methyI mande I ic acid ester and subsequent analysis of optical purity. The ozonolysis (70 %) of 119, protection of the free alcohol as the silyl ether (85 %), and reduction of the ketone with DIBAL (quant.) gave alcohol 120. Elimination of the alcohol in 120 with phosphorus oxychloride-pyridine... 

Another illustration of the use of such a biocatalytic approach was the synthesis of either enantiomer of a-bisabolol, one of these stereoisomers (out of four) which is of industrial value for the cosmetic industry. This approach was based on the diastereoselective hydrolysis of a mixture of oxirane-diastereoiso-mers obtained from (R)- or (S)-limonene [68]. Thus,starting from (S)-hmonene, the biohydrolysis of the mixture of (4S,81 S)-epoxides led to unreacted (4S,8S)-epoxide and (4S,8i )-diol. The former showed a diastereomeric purity (> 95%) and was chemically transformed into (4S,8S)-a-bisabolol. The formed diol... 

In the search for environmentally benign chemicals that might deter birds such as starlings, crows, or pigeons from roosting en masse, spices and herbs such as rosemary, cumin, and thyme look promising. In some experiments, the birds feet were immersed in oil extracts of the spices. Starlings also avoided perches treated with starch mixes of (R)-limonene, (S)-limonene, (3-pinene, or methiocarb. The first three occur in rosemaiy, cumin, and thyme (Clark, 1997). 

The stmctural complexity and biological activity of the cyathane family of diterpenes has stimulated considerable interest from synthetic chemists, as reflected in the number and diversity of approaches reported thus far [42]. Our own strategy for cyathane synthesis is based on a rhodium-catalyzed [5+2] cycloaddition. The precursor for this reaction was fashioned ultimately from commercially available and inexpensive (S)-(-)-limonene. Treatment of the ketone 139 with 5 mol% [RhCl(CO)2]2 in 1,2-dichloro-ethane gave cycloadduct 140 (Scheme 13.14) in 90% yield and in analytically pure form after simple filtration through a plug of neutral alumina [43]. 

More recently, Bachi and coworkers extended and adapted the TOCO reaction to the synthesis of 2,3-dioxabicyclo[3.3.1]nonane derivatives hke 228 (Scheme 52) ° ° . As detailed in Scheme 53a, the bridged bicyclic hydroperoxide-endoperoxides hke 229 are obtained, from (S )-limonene (227), in a 4-component one-operation free-radical domino reaction in which 5 new bonds are sequentially formed. Particular experimental conditions are required in order to reduce the formation of by-products 230 and (PhS)2, and to favor the critical 6-exo-ring closure of peroxy-radical 231 to carbon-centered radical 232206 chemoselective reduction of bridged bicyclic hydroperoxide-endoperoxides... 

Besides the synthesis of racemic dehydroiridodiol [37], some ex-chiral-pool syntheses using (S)-limonene have been described [38]. Dehydroiridodial was synthesized in the same manner [39]. Since the increasing number of cyclopentanoid natural products and their interesting biological activity has stimulated considerable interest in the synthesis of such compounds, we have used our methodology to provide a new asymmetric synthesis of dehydroiridodial, dehydroiridodiol, as well as analogues [40]. 

It was also reported that there were slight differences in the activity of enantiomers. (R)-(-i-)-Limonene and (iI)-(-t)-carvone were more biologically active than their isomers (S)-(-)-limonene and (S)-(-)-carvone [115],... 

Solanum avicu-lare and Dioscorea deltoidea (S)-(-)-Limonene, (k)-(+)-limonene Carvone [95]... 

Acetic Amyl alcohol Acetaldehyde Bornyl acetate Acetone ci s-Limonene 8-Cadinene... 

Deuterium and tritium isotope effect study of the methyl-methylene elimination in the enzyme catalyzed biosynthesis of (R)- and (S)- limonenes (506)... 

The enzyme-catalysed cyclization of (R)-[9-2Hi,3 Hi]geranyl diphosphate to (4.S )-limonene has been found to terminate predominately by re-facial, anti proton elimination at the cis methyl group of the intermediate (35)-linalyl diphosphate.80... 

Y96F/V247L Site-directed mutagenesis (+)-a-Pinene [142], (S)-limonene [143]... 

The existence of chirality in nature is of particular importance in numerous recognition processes, often illustrated by examples detectable by non-spectroscopic methods such as the different orange and lemon odors of R-(+)- and S-(-)-limonene, respectively (Fig. 3) [8]. As such, chiral discrimination is also of considerable consequence in the medical sciences, as often one enantiomer is pharmaceutically active whereas the other may show adverse side effects. A historic example is the anti-emetic activity of one of the enantiomers of thalidomide, while the other can cause fetal damage [9,10]. These considerations highlight the importance of chiral discrimination in the production of biologically active materials, whereas on the other hand, the design of routes to asymmetric synthesis presents an active challenge to synthetic chemists worldwide. 

Fig. 3 Orange and lemon odor in mirror image molecules R-(+)- and S-(-)-limonene, respectively...

S)-(-)-limonene 75 (Eq. 33) [60]. These reactions gave tetrahydrofuran derivatives as single diastereomers. 

Table 2. Diastereoselectivity of the Epoxidation of (S)-Limonene by Various Reagents...

The selectivity pattern of d° transition metal catalyzed epoxidations is much less readily understood. In the molybdenum-catalyzed epoxidation of (S)-limonene (Table 2, entries 1 and 2) the cis selectivity could perhaps be explained by a directing effect due to -coordinating of the second double bond to molybdenum. Such a selectivity is completely missing in the analogous tungsten-catalyzed reaction of (S)-limonene (Table 2, entry 4) in the absence of a second double bond as, for example, in 3/(-acetoxy-5-cholestene (Table 4) reactions with both metals afford similar diastereomeric ratios. 

Although the monocyclic terpenes a-terpinene and S-limonene have the same basic carbon skeleton [10], they reveal quite different cycloaddition behavior ... 

Scheme 2. Cycloadditions of silene 1 with a-teipinene, S-limonene, and myicene.

With S-limonene 1 yields 5 and the silacyclobutanes E/Z-6 in a ratio of 73 12 15. Compound 5 is formed by an ene reaction, which is well known for reactions of 1 with alkines [11], strained ring systems, like norbomene or norbomadiene [12], and butadienes [8]. In contrast to the reaction of 1 with isoprene (ratio E/Z-C E/Z-D E = 38 38 14 8 2) the formation of ene product 5 is favored 2D-NMR investigations prove these results [13]. 

Monoterpenes derive fi om fra 5-/ -menthane (4-isopropyl-1-methyl-cyclohexane), respectively from the unsaturated menthene, CioHig, or menthadiene, CioHie a-terpinene and S-limonene are isomeric forms of menthadiene see H. Beyer, W. Walter, Lehrbuch fur Organische Chemie, Hirzel Verlag, Stuttgart, 1984. 

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