Carvacrol, 8-hydroxy

Heating of carvone in water at 210 °C for 10 min afforded 8-hydroxy-p-menth-6-en-2-one, the equilibrium position favoring the starting material by a factor of 4 1. The hydroxymenthenone, although in equilibrium with the starting material, also underwent elimination of water and isomerization to carvacrol, giving a 1 1 1 mixture of these three substances at 230 °C after 10 min. At 250 °C, for 10 min, carvone isomerized to carvacrol almost quantitatively (Scheme 2.11) [47]. 

Ionene, a commercial fragrance, has been prepared traditionally by treatment of a- and /3-iononcs with hydriodic acid containing phosphorus or by distillative heating in the presence of 0.5% iodine. In an unoptimized demonstration, cyclization occurred more cleanly and simply by MBR with /3-ionone in water at 250 °C (Scheme 19) [83]. Work-up also was facilitated, as the need for removal of catalyst or the formation and separation of bi-products was avoided. At elevated temperature, the addition of water to olefins can occur readily, without adding catalyst. (S)-(+)-carvone in water for 10 min at 180 °C afforded optically pure 8-hydroxy-p-6-mcnlhcn-2-one as an intermediate toward carvacrol [84], Addition of water across the 8,9-double bond of carvone occurred regioselectively, by Markovnikov addition. Carvacrol itself was obtained almost quantitatively from carvone at 250 °C after 10 min (Scheme 19) [84]. 

The proofs for the above constitutions are as follows (i) Thymol yields cymene, i-methyl 4-iso-propyl benzene, by loss of the hydroxyl oxygen by means of phosphorus penta-sulphide. (2) Carvacrol may be synthesized from potassium cymene sulphonate by fusion with potassium hydroxide. Therefore both must be mono-hydroxy cymenes. (3) Thymol by means of phosphorus pentoxide splits off the iso-propyl radical yielding meta-cresol and propylene. (4) Carvacrol by the same reaction yields ortho-cresol. Therefore in thymol the hydroxy group is meta to the methyl group while in carvacrol it is ortho. The following relationships are thus established. 

Carvacrol. 2-Methyl-5-(].methylethyt)phenot 2 -p-cymenol 2-hydroxy -p-cymene isopropyl-o-cresol isothymol. C10H14O mol wt 150.21. C 79.95%, H 9.40%, O 10.65%, Found in oil of origanum, thyme, marjoram, summer savory E. Guenther, The Essential Oils vol. 2 (Van... 

Because MBR and CMR enable rapid heating and cooling of reactions, in principle they could be usefully applied to the preparation of kinetic products. A successful example with important industrial applicability is the acid-catalyzed hydrolysis of cellulose to afford practical conversions to glucose and oligosaccharides [12, 15]. Also, treatment of (S)-(+)-carvone in water for 10 min at temperatures between 180 and 250 °C, afforded 8-hydroxy-p-6-menthen-2-one as an intermediate on the pathway to carvacrol [31]. Addition of water to the 8,9 olefinic bond of carvone was regioselective and proceeded at a lower temperature than did isoaromatization (Scheme 3.11). The kinetic product was readily isolated by differential extraction from the recyclable starting ketone, affording a preparative route despite the low conversion. 

Carvacrol [2-Hydroxy-1 -methyl-4 -%aopropyl-benzene, 2-hydroxycymene, cymophenol, 4-i o-propyl-o-creaol)... 

Carvacrol (191) was biotransformed to 3-hydroxy- (470), 9 hydros (471), 7-hydroxy- (475), and 8 hydrojQ carvacrol (474), 8,9 dehydrocarvacrol (473), carvacrol 9 oic acid (472), carvacrol-7-oic acid (476), and 8,9-dihydroxycarvacrol (477) by rats (Ausgulen et al., 1987) and microorganisms (Demirci, 2000) including 71 roseum and Cladosporium sp. (Figure 19.80). Furthermore, carvacrol methyl ether (191-Me) was converted by the same fungi to give 7-hydroj - (475-Ac) and 9-hydroxy-carvacrol methyl ether (471-Mc) and 7,9-dihydroxycarvacrol methyl ether (478) (Demirci, 2000) (Figure 19.80). 

Metabolic pathways of menthol (137), menthone (149), thymol (179), and carvacrol methyl ether (202) are summarized in Figure 19.201. Menthol (137) is generally hydroxylated to give 1-hydroxy-(138), 2-hydroxy- (140), 4-hydroxy- (141), 6-hydroxy- (139), 7-hydroxy- (143), 8-hydroxy- (142), and 9-hydroxymenthol (144) and 1,8-dihydroxy- (146) and 7,8-dihydroxymenthol (148) (Asakawa et al., 1991 Takahashi et al., 1994 Van der Werf et al., 1997). Racemic menthyl acetate and menthyl chloroacetate are hydrolyzed asymmetrically by an esterase of microorganisms (Brit Patent, 1970 Moroe et al., 1971 Watanabe and Inagaki, 1977a,b). Menthone (149) is reductively metabolized to 137 and oxidatively metabolized to 3,7-dimethyl-6-hydroxyoctanoic acid (152), 3,7-dimethyl-... 

Abass et al. [132] described the metabolism of a-thujone using human hepatic preparations in vitro. Their aim also to determine the relevance of cytochrome P450 and the possible interference of other enzymes in the metabolization of a-thujone. The substance was shown to have two major metabolites (7- and 4-hydroxy-thujone) and two minor metabolites (2-hydroxy-thujone and carvacrol), and glutathione and cystein conjugates were also detected. CYP2A6 was responsible for 70-80 % of the metabolism, followed by CYP3A4 and CYP2B6. 

Some components, monoterpenes, present in the EOs obtained from plants belonging Lamiaceae family also have proved reducing hyperlipidemia and hypercholesterolemia. Thus, Carvacrol and thymol, via post-transcriptional actions, suppress 3- hydroxy-3-methylglutaryl CoA... 

Aeschbach, R., Loliger, J., Scott, B.C., Murcia, A., Butler, J., Halliwell, B., and Aruoma, O.I. 1994. Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxy-tyrosol. Food Chem. Toxicol, 32 31-36. 

Calycopterin diethyl ether. 5,4 -Diethoxy-3,6J,8-tetramethoxyflavone, 1342 Calycopterin dimethyl ether. 3,5,6,7,8,4 -Hexamethoxyflavone, 1340 Calycopterol pentamethyl ether. l-(2-Hydroxy-3,4,5,6-tetramethoxyphenyl)-2-methoxy-ethanone, 1340-1341 Carvacrol. 2-Methyl-5-isopropylphenol, 1264 Casticin. 5,3 -Dihydroxy-3,6,7,4 -tetramethoxyflavone, 131 a-Chloroacetovanillone. a-Chloro-4 -hydroxy-3 -methoxyacetophenone, 1384 Chlorflavonin. 3 -Chloro-5,2 -dihydroxy-3,7,8-trimethoxyflavone, 1335 Chlorflavonin dimethyl ether. 3 -Chloro-3,5,7,8,2 -pentamethoxyflavone, 1335 Cladrastin. 7-Hydroxy-6,3, 4 -trimethoxyisoflavone, 1505 Cladrin. 7-Hydroxy-3, 4 -dimethoxyisoflavone, 1487 Creosol. 2-Methoxy-4-methylphenol, 1242... 

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