Trans-caryophyllene

Grosjean, D., E. L. Williams, II, E. Grosjean, J. M. Andino, and J. H. Seinfeld, Atmospheric Oxidation of Biogenic Hydrocarbons Reaction of Ozone with /J-Pinene, d-Limonene, and trans-Caryophyllene, Em iron. Sci. Techriol., 27, 2754-2758 (1993a). 

Synonyms Caryophyllene (-)-trans-Caryophyllene 8-Methylene-4,11,1 l-(trimethyl) bicycle (7.2.0) undec-4-ene trans-(1R,9S)-8-Methylene-4,11,11 -trimethylbicycio [7.2.0] undec-4-ene 4,11,11-Trimethyl-8-methylene, bicycle [7.2.0] unclec-4-ene Definition A mix of sesquiterpenes occurring in many essential oils (clove oil, lavender oil, cinnamon leaves, copaiba balsam)... 

Trans-caryophyllene, the major compound of many EOs showed signi cant relaxing effects on the basal tone and on precontracted isolated rat trachea. Basal tone was only affected when the endothelium was intact. Trans-caryophyllene demonstrated signi cant relaxing effects on tracheal muscle, dependent on an induced blocked of Ca -in ux through voltage-dependent Ca -channels (Pinho-da-Silva et al., 2012). 

Pinho-da-Silva, L., Mendes-Maia, P. V., Teo lo, T. M., Barbosa, R., Caccatto, V. M., Coelho e Souza, A. N. et al. (2012). Trans-Caryophyllene, a natural sesquiterpene, causes tracheal smooth muscle relaxation through blockade of voltage-dependent Ca + channels. 17, 11965-11977. 

A fraction of American sulfate turpentine oil (0.5% of the total) consists mainly of an azeotropic mixture of anethole and caryophyllene. trans-Anethole can be isolated from this mixture by crystallization. 

Artemisia lactiflora Wallich Tian Cai (whole plant) Flavonoid glycoside, coumarin, lactiflorenol, spathulenol, s-guaiazulene, beta-guaienen, trans-(3-farnesene, frans-caryophyllene, limonene, elemene, copaene, myrcene.57 Diuretic, regulate menstruation, treat headache, high blood pressure. 

Results of detailed GC-MS analysis of these two fractions are reported in Table 17.2 (volatile oil column and waxes column). Anise waxes were formed mainly by n-pentacosane (35.7%), n-heneicosane (25.8%), n-tricosane (10.3%), n-docosane (9.0%) and n-tetracosane (6.2%). Volatile oil contained 94.2% of anethole (cis and trnns). In the oil, estragole (1.4%), limonene (1.7%), linalool (0.3%), two terpineol isomers (0.3%) and linalyl acetate (0.3%) were also present. Caryophyllene (0.5%) and trans-bergamotene (0.7%) were the main compounds among sesquiterpenes. 

Caryophyllene is the main hydrocarbon component of clove oil, from which it is produced as a by-product of eugenol extraction. The endocyclic double bond of caryophyllene is highly strained and reacts readily with a variety of reagents. Usually both double bonds become involved in a trans-annular reaction, followed by rearrangements to give mixtures of polycyclic products. Some of these mixtures find use as woody ingredients in perfumes. Caryophyllene and two typical reaction products from it are shown in Scheme 4.29. 

Materials. Trans-stilbene (Fluka AG) and (+)-a-pinene (Aldrich Chemical Company) were used as received C -stilbene and perisobutyric acid (PIBAC) were prepared as described in [19], (-)-Caryophyllene (>99%) and eugenol (95%) were isolated from the oil of Eugenia caryopyllata by vacuum rectification. (+)-3-Carene (95%) and dipentene [( )-limonene, 95%] were prepared by rectification of the Pinus sylvestris turpentine. 

Qccurance and Identification. An early report of cotton volatile composition by Minyard et al. (44) involved steam distillation of large quantities of leaves and flowers. Major compounds identified included the monoterpenes a-pinene, B-pinene, myrcene, trans-B-ocimene, and limonene ( 4). Several other monoterpene hydrocarbons were also present in low concentration. Since that report, many other terpenes have been identified in cotton essential oil steam distillates and solvent extracts. These compounds include cyclic hydrocarbons such as bisabolene, caryophyllene, copaene and humulene (45-47), the cyclic epoxide caryophyllene oxide (45), cyclic alcohols such as bisabolol, spathulenol, and the aromatic compound... 

Carbon suboxide, 52 Carbonylation, 148, 149, 216 Carbonyl chlorofluoride, 48, 54 Carbonyl cyanide, 60-61 N,N -Carbonyldiimidazole, 61 1,1-Carbonyldi-l,2,4-triazole, 61 N-Carbonylsulfamic acid chloride (N-Carbonylsulfamyl chloride), 61 Carboxamides, 270 Carboxamine-N-sulfochlorides, 70 p-Carboxybenzenediazonium chloride, 62 p-Carboxybenzenesulfonazide, 62 Carboxylation, 15, 16 Carboxylic acid anhydrides, 133 Carboxylic acid N,N-dimethylamines, 153 Carboxylic anhydrides, 409-410 p-Carboxyphenylhydrazones, 62 Cardenolides, 130, 131 (S-Carotene, 19 /-Carvone, 451, 452 i//-Caryophyllene, 149, 150 Catechol, 65, 233 Catechol amines, 159 Catechyl phosphorus tribromide, 63 Catechyl phosphorus trichloride, 63 Cis-Cecropia juvenile hormone, 261 Cedrene, 234, 235 a-Cedrene, 349 /3-Cedrene, 349 Cendranoxide, 234, 235 Cephalosporin C, 48 Ceric ammonium nitrate, 63-65 Ceric sulfate. 65 Cesium fluoride, 346 trans-Chalcone oxide, 422 Chalcone phenylhydrazones, 257, 258 Chalcones, 406 Chloramine, 65-66, 69 Chloranil, 66-67, 113, 116, 401,454... 

Humulene biosynthesis probably involves the intermediacy of a monocyclic carbonium ion or its biological equivalent [c/. (303)] derived from trans,trans-farnesyl pyrophosphate (16), A recent investigation based on this idea has shown that treatment of the ( , )-mesylate (303 Z=OMs) with dime thy laluminium phenoxide provides humulene (304) in excellent yield. The corresponding (Z, )-isomer, when treated with di-isobutylaluminium 2,6-dibutyl-4-methyl-phenoxide, is efficiently converted into germacrene (307) whereas the E,E)-isomer under these conditions provides a mixture (2 1) of humulene (304) and germacrene A (305). Monohydroboration-oxidation of caryophyllene... 

As mentioned in Chapter 2, these molecules all suffer a high level of strain in the rings. Medium sized rings experience steric strain and the introduction of trans double bonds increases this significantly. This stored energy has dramatic effects on the chemistry of the caryophyllenes and humulenes as we shall see. 

The greatest problem in synthesising caryophyllene lies, not surprisingly, in the construction of the nine-membered ring and its trans double bond. This would be exceptionally difficult to achieve by any cyclisation reaction and so Corey chose to tackle it by fragmentation of a bicyclic system. The fragmentation step is the key feature of his synthesis but first let us look at how he constructed the substrate for it. This scheme is shown in Figure 7.30. 

Treatment of hydroxytosylate (7.155) with base leads, as discussed, to the bicyclic ketone (7.159) which contains the nine-membered ring and trans-double bond required for caryophyllene. Epimerisation back to the trans-ring fusion and subsequent Wittig reaction of the resultant ketone... 

Normally 1,1-disubstituted double bonds react faster with protons than do 1,1,2-trisubstituted ones because the former are more polarisable, a feature which protons prefer. However, in the case of caryophyllene, the endocyclic trans double bond is so strained that the normal reactivity pattern is reversed and it is this bond which is protonated first. In Figure 7.35, protonation of the endocyclic double bond is rapidly followed by addition of the electrons of the exocyclic bond to give the tricyclic carbocation (7.164). As would be expected, in both instances, the electrophile is added to the less substituted end of the olefin. The carbocation can be trapped by water to give the alcohol (7.165) which is known both as caryophyllene alcohol and caryolanol. Alternatively, a 1,2-carbon shift can occur to reduce strain... 

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