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Pseudomonas putida F1 utilizes p-cymene (p-isopropyltoluene) by an 11-step pathway through p-cumate (p-isopropylbenzoate) to isobutyrate, pyruvate, and acetyl coenzyme A. The cym operon, encoding the conversion of p-cymene to p-cumate, is located just upstream of the cmt operon, which encodes the further catabolism of p-cumate and is located, in turn, upstream of the tod (toluene catabolism) operon in P. putida F1. The sequences of an 11,236-bp DNA segment carrying the cym operon and a 915-bp DNA segment completing the sequence of the 2,673-bp DNA segment separating the cmt and tod operons have been determined and are discussed here. The cym operon contains six genes in the order cymBCAaAbDE. The gene products have been identified both by functional assays and by comparing deduced amino acid sequences to published sequences. Thus, cymAa and cymAb encode the two components of p-cymene monooxygenase, a hydroxylase and a reductase, respectively; cymB encodes p-cumic alcohol dehydrogenase; cymC encodes p-cumic aldehyde dehydrogenase; cymD encodes a putative outer membrane protein related to gene products of other aromatic hydrocarbon catabolic operons, but having an unknown function in p-cymene catabolism; and cymE encodes an acetyl coenzyme A synthetase whose role in this pathway is also unknown. Upstream of the cym operon is a regulatory gene, cymR. By using recombinant bacteria carrying either the operator-promoter region of the cym operon or the cmt operon upstream of genes encoding readily assayed enzymes, in the presence or absence of cymR, it was demonstrated that cymR encodes a repressor which controls expression of both the cym and cmt operons and is inducible by p-cumate but not p-cymene. Short (less than 350 bp) homologous DNA segments that are located upstream of cymR and between the cmt and tod operons may have been involved in recombination events that led to the current arrangement of cym, cmt, and tod genes in P. putida F1.
The addition reactions of the 16e half-sandwich complexes [M(eta5-Cp*)[E2C2(B10H10)]] (Cp*=pentamethylcyclopentadienyl: 1S: E=S, M=Rh; 2S: E=S; M=Ir; 2Se: E=Se, M=Ir) and [M(eta6-p-cymene)[S2C2(B10H10)]] (p-cymene=4-isopropyltoluene; 3S: M=Ru; 4S: M=Os), with acetylene, propyne, and 3-methoxypropyne lead to the 18e complexes 5-19 with a metal-boron bond in each case. The reactions start with an insertion of the alkyne into one of the metal-chalcogen bonds, followed by B-H activation, transfer of one hydrogen atom from the carborane via the metal to the terminal carbon of the alkyne, and concomitant ortho-metalation of the carborane. The E-eta2-CC and the C(1)B units are arranged either cisoid or transoid at the metal. X-ray structural analyses are reported for one of the starting 16e complexes (4S), the cisoid complex 12S (from 2S and HC[triple bond]C-CH3), and the transoid complexes 9S and 14S (from 1S and HC[triple bond]C-CH2OMe, and from 3S and HC[triple bond]CH, respectively). All new complexes 5-19 were characterized by NMR spectroscopy (1H, 11B, 13C, and 77Se and 103Rh NMR spectroscopy when appropriate).
The easy synthesis of [Sb2W20O70{Ru(p-cymene)}2](10-) by the reaction between the organometallic precursor [Ru(p-cymene)Cl2]2 and [Sb2W20O70]14-, formed in situ, confirms the importance of the organometallic route to well defined ruthenium(+II)-substituted heteropolytungstates.
The reactions of the 16e half-sandwich complexes [Cp*M[S2C2(B10)H10)]] (1: M=Rh; 2: M = Ir) and [eta6-(4-isopropyltoluene)M[S2C2(B10H10)] (3: M=Ru; 4: M=Os) with both methyl acetylene monocarboxylate and dimethyl acetylene dicarboxylate were studied in order to obtain more evidence for B-H activation, ortho-metalation, and B(3,6)-substitution of the carborane cluster. In the case of rhodium, the reaction of 1 with methyl acetylene monocarboxylate led to new complexes after twofold insertion into one of the Rh-S bonds (7), and twofold insertion together with B-substitution at the carborane cage (8). In the case of iridium, the reactions of 2 with methyl acetylene monocarboxylate gave two geometrical isomers 10 and 11, in which the alkyne is inserted into one of the Ir-S bonds, followed by hydrogen transfer from the carborane via the metal to the former alkyne and formation of an Ir-B bond. Only one type each (12 and 13) of these isomers was obtained from the reactions of the ruthenium and osmium half-sandwich complexes 3 and 4. The 16e starting materials 1-4 reacted with dimethyl acetylene dicarboxylate at room temperature to give the complexes 14-17, respectively, which are formed by addition of the C=C bond to the metal center and insertion into one of the metal-sulfur bonds. The proposed structures in solution were deduced from NMR data (1H, 11B, 13C, 103Rh NMR), and X-ray structural analyses were carried out for the rhodium complexes 7 and 8.
The capability of nitrate-reducing bacteria to degrade alkyltoluenes in the absence of molecular oxygen was investigated with the three isomers of xylene, ethyltoluene, and isopropyltoluene (cymene) in enrichment cultures inoculated with freshwater mud. Denitrifying enrichment cultures developed most readily (within 4 weeks) with p-cymene, a natural aromatic hydrocarbon occurring in plants, and with m-xylene (within 6 weeks). Enrichment of denitrifiers that utilized m-ethyltoluene and p-ethyltoluene was slow (within 8 and 12 weeks, respectively); no enrichment cultures were obtained with the other alkylbenzenes within 6 months. Anaerobic degradation of p-cymene, which has not been reported before, was studied in more detail. Two new types of denitrifying bacteria with oval cells, strains pCyN1 and pCyN2, were isolated; they grew on p-cymene (diluted in an inert carrier phase) and nitrate with doubling times of 12 and 16 h, respectively. Strain pCyN1, but not strain pCyN2, also utilized p-ethyltoluene and toluene. Both strains grew with some alkenoic monoterpenes structurally related to p-cymene, e.g., alpha-terpinene. In addition, the isolates utilized p-isopropylbenzoate, and mono- and dicarboxylic aliphatic acids. Determination of the degradation balance of p-cymene and growth with acetate and nitrate indicated the capacity for complete oxidation of organic substrates under anoxic conditions. Adaptation studies with cells of strain pCyN1 suggest the existence of at least two enzyme systems for anaerobic alkylbenzene utilization, one metabolizing p-cymene and p-ethyltoluene, and the other metabolizing toluene. Excretion of p-isopropylbenzoate during growth on p-cymene indicated that the methyl group is the site of initial enzymatic attack. Although both strains were facultatively aerobic, as revealed by growth on acetate under air, growth on p-cymene under oxic conditions was observed only with strain pCyN1. Strains pCyN1 and pCyN2 are closely related to members of the Azoarcus-Thauera cluster within the beta-subclass of the Proteobacteria, as revealed by 16S rRNA gene sequence analysis. This cluster encompasses several described denitrifiers that oxidize toluene and other alkylbenzenes.
The first carbonyl free ruthenium/low valent Group 13 organyl complexes are presented, obtained by insertion of ER (ER = GaCp*, InCp*, In[C(SiMe(3))(3)]) into the Ru-Cl bonds of [(p-cymene)RuCl2]2, [Cp*RuCl]4 and [Cp*RuCl2]2. The compound [(p-cymene)RuCl2]2 reacts with GaCp*, giving a variety of isolated products depending on the reaction conditions. The Ru-Ru dimers [{(p-cymene)Ru}2(GaCp*)4(mu3-Cl)2] and the intermediate [{(p-cymene)Ru}2(mu-Cl)2] were isolated, as well as monomeric complexes [(p-cymene)Ru(GaCp*)3Cl2], [(p-cymene)Ru(GaCp*)2GaCl3] and [(p-cymene)Ru(GaCp*)2Cl2(DMSO)]. The reaction of [Cp*RuCl]4 with ER gives "piano-stool" complexes of the type [Cp*Ru(ER)3Cl](ER = InCp*, In[C(SiMe3)3], GaCp*. The chloride ligand in complex can be removed by NaBPh4, yielding [Cp*Ru(GaCp*)3]+[BPh4]-. The reaction of [Cp*RuCl2]2 with GaCp* however, does not lead to an insertion product, but to the ionic Ru(II) complex [Cp*Ru(GaCp*)3]+[Cp*GaCl3]-. The ER ligands in complexes 3, 5, 6, 7 and 8 are equivalent on the NMR timescale in solution due to a chloride exchange between the three Group 13 atoms even at low temperatures. The solid state structures, however, exhibit a different structural pattern. The chloride ligands exhibit two coordination modes: either terminal or bridging. The new compounds are fully characterized including single crystal X-ray diffraction. These results point out the different reactivities of the two precursors and the nature of the neutral p-cymene and the anionic Cp* ligand when bonding to a Ru(II) centre.
The fumigant toxicity of the essential oil component p-cymene was assessed against Western Flower Thrips, Frankliniella occidentalis. F occidentalis adult females, first- and second-instar larvae and eggs were exposed for 2, 24 and 48 h to combinations of three p-cymene doses and two carbon dioxide levels (ambient, 10%). Additional experiments were conducted on F occidentalis adult females with lower carbon dioxide levels (ambient, 2%, 4%, 6%) applied in combination with p-cymene. Combined applications of p-cymene and carbon dioxide were found to increase significantly the fumigant toxicity of p-cymene against both adult female and larval thrips, but not thrips eggs. An increase in exposure time also led to an increase in adult and larval mortalities in both the p-cymene alone and combined treatments. These results indicate that by combining applications of the essential oil component, p-cymene, with increased carbon dioxide, it may be possible to achieve toxicity levels similar to those of standard chemical fumigants.
Three ruthenium sulfide clusters with labile CH3CN ligands have been photochemically synthesized. Irradiation of [(cymene)3Ru3S2](PF6)2 ([1](PF6)2) in CH3CN gives [(cymene)2(CH3CN)3Ru3S2](PF6)2 ([2](PF6)2), which has been characterized by 1H NMR spectroscopy, ESI mass spectrometry, and chemical reactivity. Treatment of [2](PF6)2 with PPh3 gives [(cymene)2(CH3CN)2(PPh3)Ru3S2](PF6)2 ([3](PF6)2) and [(cymene)2(CH3CN)(PPh3)2Ru3S2](PF6)2 ([4](PF6)2), while treatment with 1,4,7-trithiacyclononane (9S3) gives [(cymene)2(9S3)Ru3S2](PF6)2 ([5](PF6)2). A crystallographic study demonstrated that the Ru3 core in [3](PF6)2, [4](PF6)2, and [5](PF6)2 is distorted with a pair of elongated Ru-Ru bonds. Cyclic voltammetry shows that [3](PF6)2 and [4](PF6)2 undergo two closely spaced reversible one-electron reductions whereas [5](PF6)2 undergoes one irreversible one-electron reduction and one reversible one-electron reduction. Prolonged irradiation of [1](PF6)2 in CH3CN causes decomposition, resulting in the pentanuclear cluster [(cymene)4Ru5S4](PF6)2 ([6](PF6)2).
Isotope ratio mass spectrometry online coupled with capillary gas chromatography (GC-Py-IRMS) on column INNOWAX is used in the origin specific analysis and the authenticity control of the phenolic essential oils (EOs). Isotopic data delta(2)H(V-SMOW) of thymol and carvacrol in natural essential oils were evidently more depleted than synthetic products (from -49 to 7 per thousand for thymol and -61 per thousand for carvacrol). delta(2)H(V-SMOW) values of p-cymene, gamma-terpinene and thymol in authentic thyme oils (Thymus vulgaris L. and Thymus zygis L.) were found from -300 to -270 per thousand, from -285 to -248 per thousand and from -259 to -234 per thousand, respectively. delta(2)H(V-SMOW) values of carvacrol and p-cymene in authentic oregano oils (Origanum heracleoticum L., Coridothymus capitatus L. and Origanum compactum L.) varied from -223 to -193 per thousand and from -284 to -259 per thousand, respectively. For authentic Satureja montana subsp. montana essential oils, the mean delta(2)H(V-SMOW) value for aromatic compounds were found to be the following: gamma-terpinene -273 per thousand (SD=4.6 per thousand) and p-cymene -283 per thousand (SD=3.0 per thousand), thymol -245 per thousand (SD=1.8 per thousand) and carvacrol -226 per thousand (SD=1.7 per thousand). In addition, p-cymene was previously found as a precursor of the biosynthesis of thymol and carvacrol in thyme oil, thus, we considered p-cymene as an endogenous reference compound (ERC) for D/H ratio analysis. The isotopic fractionation factors alpha(thymol/p-cymene)=1.05 and alpha(carvacrol/p-cymene)=1.08 were obtained and also used to control the authenticity of the phenolic EOs.
Several classes of mutants of Pseudomonas putida (JT810) defective in the utilization of p-cymene as sole carbon source have been isolated. Selective enrichment of the mutants and for strains putatively cured of a degradative plasmid was achieved by incubation of cells in minimal growth media containing p-cymene (or p-cumate) and various halogenated analogs of the growth substrates or pathway intermediates. Analogs which led to successful enrichments included: p-chlorotoluene, p-bromotoluene, alpha-chloro-p-xylene, and p-iodobenzoate. A mutant strain, PpJT811, constitutive for the p-cymene pathway gave significantly greater enrichments of defective mutants than the wild-type parent PpJT810 after incubation with the halogenated analogs. It is suggested that the defective mutants are enriched because of the genetic alterations they possess, which confer immunity to a lethal synthesis performed by transformation of the analogs in clones possessing an intact p-cymene pathway. A nomenclature for the genetic organization of p-cymene pathway is described.
BACKGROUND: Outbreaks of food poisoning associated with drinking un-pasteurised apple juice contaminated with enterohaemorrhagic Escherichia coli O157:H7 are a cause of serious illness and occasionally death. Whilst a well-established heat process (pasteurisation) will readily eliminate the pathogen, some consumers are demanding more fresh-like foods that have not been subjected to processing methods that are perceived as severe and may lead to loss of flavour and vitamins. Therefore, alternative methods are being investigated to replace pasteurisation and improve the safety of minimally-processed juices. The addition of natural antimicrobial substances such as the phenolic substances carvacrol and p-cymene (derived from the essential oils of herbs and spices) provides a potential new route to assure safety and extend the shelf-life of raw fruit juices. The aim of this study was to evaluate the addition of very low concentrations (0.25-1.25 mM) of carvacrol and p-cymene both individually and in combination as a novel means of controlling Escherichia coli O157:H7 in un-pasteurised apple juice. RESULTS: When inoculated at a level of 4 log CFU/ml into un-pasteurised apple juice (pH 3.20 +/- 0.06), Escherichia coli O157:H7 survived for up to 3 and 19 days at 25 degrees and 4 degrees C, respectively. Treatment of the juice with 1.25 mM carvacrol or p-cymene reduced the numbers of E. coli O157:H7 to undetectable levels within 1-2 days at both storage temperatures. The effective concentrations of carvacrol could be reduced even further by combining it at 0.5 mM with cymene at 0.25 mM. The phenolic compounds were biocidal against both spoilage yeasts and E. coli O157:H7 thereby increasing the shelf-life and improving the safety of un-pasteurised apple juice, particularly when stored at chill temperatures. CONCLUSION: The results showed that the natural antimicrobial compounds carvacrol and p-cymene could potentially be used to extend the shelf life and improve the safety margins in un-pasteurised chilled fruit juices.
The antibacterial action of carvacrol and cymene on two Listeria monocytogenes strains (STCC4031 and NCTN4032) was studied. Carvacrol or cymene showed inhibitory effect on the growth of L. monocytogenes during lag and exponential growth phases and was more evident with increasing concentrations in brain heart infusion broth at 30 degrees C. Carvacrol or cymene also decreased the survival of mid-exponential-growth-phase L. monocytogenes STCC4031 cells in potassium-N-2-hydroxy-ethylpiperazine-N-ethanesulfo nic acid, at 30 degrees C. The combination of carvacrol and cymene resulted in an increased antibacterial effect on the growth and a synergistic effect on the viability of L. monocytogenes compared with the natural compounds applied separately. The analysis of survival curves by the Weibull frequency distribution function allowed an accurate prediction of the level of inactivation achieved. Interestingly, an important bactericidal effect (4.7-log reduction) of low concentrations of both antimicrobials combined (0.75 mM) was observed on L. monocytogenes in carrot juice. This study indicates the potential use of carvacrol and cymene applied simultaneously for preservation of minimally processed foods.
1. p-Cymene is an aromatic monoterpene found in the leaves of Eucalyptus spp. and is ingested in the diet of two marsupial folivores, the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus). The metabolism of p-cymene by liver microsomes from the possum, koala and rat (an animal whose diet is not terpene-rich) was examined. 2. The major p-cymene metabolite in each species was cuminyl alcohol, with smaller amounts of other side-chain alcohols being formed. No phenolic metabolites were detected. Possum and koala microsomes further oxidized cuminyl alcohol to cumic acid. 3. Pretreatment with a terpene diet more than doubled the V(max) for cuminyl alcohol formation by possum microsomes. This is similar to a previous finding by our group with 1,8-cineole and indicates that a terpene-containing diet results in induction of the enzymes responsible for terpene metabolism. 4. The rank order of the ability to metabolize p-cymene, measured by intrinsic clearance (Cl(int) = V(max)/K(m) [microl mg protein(-1) min(-1)]) was: terpene-treated possum (128)>control possum (107)>koala (69)>rat (38). 5. The findings support the hypothesis that animals that have adapted to a diet of Eucalypus leaf have a greater capacity than generalist feeders to metabolize dietary terpenes.
Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol (PCMC), Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, Chlorothymol, o-Cymen-5-ol, and Carvacrol are substituted phenols used as cosmetic biocides/preservatives and/or fragrance ingredients. Only PCMC, Thymol, and o-Cymen-5-ol are reported to be in current use, with the highest concentration of use at 0.5% for o-Cymen-5-ol in perfumes. The use of PCMC in cosmetics is restricted in Europe and Japan. Cresols can be absorbed through skin, the respiratory tract, and the digestive tract; metabolized by the liver; and excreted by the kidney as glucuronide and sulfate metabolites. Several of these cresols increase the dermal penetration of other agents, including azidothymidine. In acute oral toxicity studies, LD50 values were in the 200 to 5000 mg/kg day-1 range across several species. In short-term studies in rats and mice, an o-Cresol, m-Cresol, p-Cresol or m-Cresol/p-Cresol mixture at 30,000 ppm in the diet produced increases in liver and kidney weights, deficits in liver function, bone marrow hypocellularity, irritation to the gastrointestinal tract and nasal epithelia, and atrophy of female reproductive organs. The no observed effect levels (NOEL) of o-Cresol was 240 mg/kg in mink and 778 mg/kg in ferrets in short-term feeding studies, with no significant dose-related toxicity (excluding body weight parameters). In mice, 0.5% p-Cresol, but neither m-Cresol nor o-Cresol, caused loss of pigmentation. Short-term and subchronic oral toxicity tests performed with various cresols using mice, rats, hamsters, and rabbits resulted in no observed adverse effect levels (NOAELs) for mice of 625 ppm and rats of 50 mg/kg day-1, although the NOEL was 2000 ppm in a chronic study using rats. In rabbits, < or =160 mg/kg PCMC was found to produce irritation and erythema, but no systemic effects. Hamsters dosed with 1.5% p-Cresol in diet for 20 weeks had a greater incidence of mild and moderate forestomach hyperplasia as compared to the control. Acute inhalation toxicity studies using rats yielded LC50 values ranging from >20 mg/m(3) for o-Cresol to >583 mg/m(3) for PCMC. No deaths were recorded in mice given o-Cresol at 50 mg/m(3). Cats exposed (short-term) to 9 to 50 mg/m(3) of o-Cresol developed inflammation and irritation of the upper respiratory tract, pulmonary edema, and hemorrhage and perivascular sclerosis in the lungs. Rats exposed (subchronic) to o-Cresol at 9 mg/m(3) had changes in leukocytes, spinal cord smears, nervous activity, liver function, blood effects, clinical signs, and neurological effects. In guinea pigs, exposure to 9 mg/m(3) produced changes in hemoglobin concentrations and electrocardiograms (EKGs). Rats exposed (subchronic) to 0.05 mg/m(3) Mixed Cresols by inhalation exhibited central nervous system (CNS) excitation, denaturation of lung protein, and decreased weight gain. All cresols appear to be ocular irritants. Numerous sensitization studies have been reported and most positive reactions were seen with higher concentrations of Cresol ingredients. Developmental toxicity is seen in studies of m-Cresol, o-Cresol, and p-Cresol, but only at maternally toxic levels. In a reproductive toxicity study of a mixture of m-Cresol and p-Cresol using mice under a continuous breeding protocol, 1.0% caused minimal adult reproductive and significant postnatal toxicity in the presence of systemic maternal toxicity. The o-Cresol NOAEL was 0.2% for both reproductive and general toxicity in both generations. Cresol ingredients were generally nongenotoxic in bacterial, fruit fly, and mammalian cell assays. Thymol did not induce primary lung tumors in mice. No skin tumors were found in mice exposed dermally to m-Cresol, o-Cresol, or p-Cresol for 12 weeks. In the trypthan blue exclusion assay, antitumor effects were observed for Thymol and Carvacrol. Clinical patch testing with 2% PCMC may produce irritant reactions, particularly in people with multiple patch test reactions, that are misinterpreted as allergic responses. o-Cresol, p-Cresol, Thymol, Carvacrol, and o-Cymen-5-ol caused no dermal irritation at or above use concentrations. In two predictive patch tests, PCMC did not produce a sensitization reaction. Overall, these ingredients are not significant sensitizing or photosensitizing agents. The Cosmetic Ingredient Review (CIR) Expert Panel noted some of these ingredients may increase the penetration of other cosmetic ingredients and advised cosmetic formulators to take this into consideration. The CIR Expert Panel concluded that the toxic effects of these ingredients are observed at doses higher than would be available from cosmetics. A concentration limitation of 0.5% was chosen to ensure the absence of a chemical leukoderma effect. For p-Cresol and Mixed Cresols (which contain p-Cresol), the Panel considered that the available data are insufficient to support the safety of these two ingredients in cosmetics. Studies that would demonstrate no chemical leukoderma at concentrations of use of p-Cresol and Mixed Cresols, or would demonstrate a dose response from which a safe concentration could be derived, are needed.
Two Pseudomonas strains (PpG777 and PaG158) were derived from the parent isolate Pseudomonas incognita (putida). Strain PpG777 resembles the parental culture in growth on linalool as a source of carbon and slight growth on p-cymene, whereas PaG158 grows well on p-cymene, but not on linalool or other terpenes tested, and has a P. aeruginosa phenotype. Curing studies indicate that linalool metabolism is controlled by an extrachromosomal element whose loss forms a stable strain PaG158 with the p-cymene growth and P. aeruginosa phenotype characters. The plasmid can be transferred by PpG777 to both P. putida and P. aeruginosa strains. Surprisingly, the latter assume the P. putida phenotype. We conclude that the genetic potential to oxidize p-cymene is inherent in PpG777 but expression is repressed. Similarly, this observation implies that support of linalool oxidation effectively conceals the P. aeruginosa character.
The biotransformation of (+)-, (-)-, and (+-)-alpha-pinenes, (-)-beta-pinene (nopinene), (-)-cis-pinane, (+)-3-carene, (-)-cis-carane, myrcene, and p-cymene in rabbits was investigated. The major metabolites were as follows: (-)-trans-verbenol from (+)-, (-)-, and (+/-)-alpha-pinenes; (-)-10-pinanol and (-)-1-p-menthene-7,8-diol from (-)-beta-pinene; (-)-alpha-terpineol and (-)-trans-sobrerol from (-)-cis-pinane; (-)-m-mentha-4,6-dien-8-ol, 3-caren-9-ol, (-)-3-carene-9-carboxylic acid, and 3-carene-9,10-dicarboxylic acid from (+)-3-carene; carane-9,10-dicarboxylic acid from (-)-cis-carane; and myrcene-3(10)-glycol, myrcene-1,2-glycol, uroterpenol, and p-cymene-9-carboxylic acid from p-cymene. These metabolisms include allylic oxidation, epoxidation, stereoselective gem-dimethyl hydroxylation and its oxidation, cleavage of a conjugated double bond by epoxidation, and regioselective oxidation, some of which are not found usually in chemical reactions, and due to which various new compounds were determined. This biotransformation of the monoterpene hydrocarbons gave some insect pheromones in high yield.U
p-Cymene (1) was metabolized in rabbits and the following four optically active metabolites, 2-(p-tolyl)-1-propanol (3': R/S = 65:35), 2-(p-tolyl)propanoic acid (5': R/S = 0:100), p-(2-hydroxy-1-methylethyl)benzoic acid (6': R/S = 91:9) and p-(1-carboxyethyl)benzoic acid (8': R/S = 30:70), were isolated in addition to three optically inactive metabolites, 2-(p-tolyl)-2-propanol (2), p-isopropylbenzoic acid (4'), and p-(1-hydroxy-1-methylethyl)benzoic acid (7'). The presumed metabolic pathways of p-cymene in rabbits were confirmed by the administration of the intermediate metabolites (2, 3', 4', and 5'). The enantiomeric ratios of the metabolites, 3' and 6', suggested that omega-hydroxylations of the isopropyl group in 1 and 4' occurred preferentially at the pro-S methyl group. In the metabolism of 1, the S-isomers are predominant in the propanoic acid derivatives, but the R-isomers are rich in the propanol derivatives. It is of interest that the metabolism of 4', however, produced predominantly the corresponding propanol derivative (6'; R/S = 91:9) and propanoic acid derivative (8'; R/S = 80:20) possessing the same R-configuration. Some optically active p-cymene derivatives were also synthesized as standard compounds.