3,4,5-Trimethoxytoluene

The Relative Content and Distribution of Absorbed Volatile Organic Compounds in Rats Administered Asari Radix et Rhizoma Are Different between Powder- and Decoction-Treated Groups.[Pubmed:32992581]

Molecules. 2020 Sep 27;25(19):4441.

Asari Radix et Rhizoma (ARR) is an important traditional Chinese medicine. Volatile organic compounds (VOCs) are the main active constituents of ARR. Research on the metabolite profile of VOCs and the difference of absorbed constituents in vivo after an administration of ARR decoction and powder will be helpful to understand the pharmacological activity and safety of ARR. In this study, headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) was applied to profile the VOCs from ARR in rats in vivo. A total of 153 VOCs were tentatively identified; 101 were original constituents of ARR (98 in the powder-treated group and 43 in the decoction-treated group) and 15 were metabolites, and their metabolic reactions were mainly oxidation and reduction, with only two cases of methylation and esterification, and 37 unclassified compounds were identified only in the ARR-treated group. Of the 153 VOCs identified, 131 were reported in rats after oral administration of ARR for the first time, containing 79 original constituents, 15 metabolites, and 37 unclassified compounds. In the powder-treated group, methyleugenol, safrole, 3,5-dimethoxytoluene (3,5-DMT), 2,3,5-trimethoxytoluene (2,3,5-TMT), and 3,4,5-Trimethoxytoluene (3,4,5-TMT) were the main absorbed constituents, the relative contents of which were significantly higher compared to the decoction-treated group, especially methyleugenol, safrole, and 3,5-DMT. In the decoction-treated group, 3,4,5-TMT, 2,3,5-TMT, kakuol, and eugenol were the main constituents with a higher content and wider distribution. The results of this study provide a reference for evaluating the efficacy and safety of ARR.

Synthesis of coenzyme Q(0) through divanadium-catalyzed oxidation of 3,4,5-trimethoxytoluene with hydrogen peroxide.[Pubmed:28362448]

Dalton Trans. 2017 Apr 19;46(16):5202-5209.

The selective oxidation of methoxy/methyl-substituted arenes to the corresponding benzoquinones has been first realized using aqueous hydrogen peroxide as a green oxidant, acid tetrabutylammonium salts of the gamma-Keggin divanadium-substituted phosphotungstate [gamma-PW(10)O(38)V(2)(mu-O)(2)](5-) (I) as a catalyst, and MeCN as a solvent. The presence of the dioxovanadium core in the catalyst is crucial for the catalytic performance. The reaction requires an acid co-catalyst or, alternatively, a highly protonated form of I can be prepared and employed. The industrially relevant oxidation of 3,4,5-Trimethoxytoluene gives 2,3-dimethoxy-5-methyl-1,4-benzoquinone (ubiquinone 0 or coenzyme Q(0), the key intermediate for coenzyme Q(10) and other essential biologically active compounds) with 73% selectivity at 76% arene conversion. The catalyst retains its structure under turnover conditions and can be easily recycled and reused without significant loss of activity and selectivity.

[Quantitative determination of seven major absorbed volatile constituents in mice brain, liver and blood after intragastric administration of Asari Radix et Rhizoma suspension by headspace-solid phase microextraction-gas chromatography-mass spectrometry].[Pubmed:28861975]

Zhongguo Zhong Yao Za Zhi. 2016 Jan;41(2):285-293.

A headspace-solid phase microextraction-gas chromatography-mass spectrometry method（HS-SPME-GC-MS） was adopted for the quantitative study of 4-allylanisole, methyl eugenol, 2,3,5-trimethoxytoluene, 3,4,5-Trimethoxytoluene, sarisan, 3,5-dimethoxytoluene and safrole in mice brain, liver tissues and blood after intragastric administration of Asari Radix et Rhizoma. A VF-WAXms (30 mx0.25 mm, 0.25 mum film thickness) capillary column and SPME fiber coated with 65 mum polydimethylsiloxane/divinylbenzene (PDMS/DVB) were used. The calibration curves of seven volatile constituents were established to validate the method's stability (RSD<15%), repeatability (RSD<9.5%), accuracy (RSD<22%), relative recovery (87.0%-108%) and extraction recovery (74.9%-102%). The validated HS-SPME-GC-MS assay was applied to determine the concentrations of seven constituents in liver, brain and blood. The detected contents were 0.22,0.14 mug*g(-)(1),0.25 mg*L(-)(1) (4-allylanisole), 1.1, 0.39 mug*g(-)(1), 0.69 mg*L(-)(1) (methyl eugenol), 0.45, 0.13 mug*g(-)(1), 0.54 mg*L(-)(1) (2,3,5-trimethoxytoluene), 0.51, 0.15 mug*g(-)(1), 0.45 mg*L(-)(1) (3,4,5-Trimethoxytoluene), 0.48, 0.039 mug*g(-)(1), 0.69 mg*L (-)(1) (sarisan), 2.2, 1.2 mug*g(-)(1), 1.5 mg*L(-)(1) (3,5-dimethoxytoluene) and 1.3, 0.67 mug*g(-)(1), 1.1 mg*L(-)(1) (safrole) respectively. This HS-SPME-GC-MS method is rapid and convenient, with a small sample size, and applicable for the analysis and determination of volatile constituents in traditional Chinese medicines, which provides scientific data for further studies on effective substances and toxic substances in Asari Radix et Rhizoma.

Acaricidal activity of Asarum heterotropoides root-derived compounds and hydrodistillate constitutes toward Dermanyssus gallinae (Mesostigmata: Dermanyssidae).[Pubmed:26708137]

Exp Appl Acarol. 2016 Apr;68(4):485-95.

The acaricidal activity of Asarum heterotropoides root-derived principles, methyleugenol, safrole, 3-carene, alpha-asarone, pentadecane and A. heterotropoides root steam distillate constituents was tested against poultry red mites Dermanyssus gallinae (De Geer). All active principles were identified by spectroscopic analysis. Results were compared with those of two conventional acaricides, benzyl benzoate and N,N-diethyl-3-methylbenzamide (DEET). Methyleugenol (24 h LC50 = 0.57 microg/cm(2)) and safrole (24 h LC50 = 8.54 microg/cm(2)) were the most toxic compounds toward D. gallinae, followed by 3,4,5-Trimethoxytoluene, 3,5-dimethoxytoluene, estragole, alpha-terpineol, verbenone, eucarvone, linalool, and terpinen-4-ol (LC50 = 15.65-27.88 microg/cm(2)). Methyleugenol was 16.7x and 11.0x more toxic than benzyl benzoate (LC50 = 9.52 mug/cm(2)) and DEET (LC50 = 6.28 mug/cm(2)), respectively; safrole was 1.1x and 0.73x more toxic. Asarum heterotropoides root-derived materials, particularly methyleugenol and safrole, merit further study as potential acaricides. Global efforts to reduce the level of highly toxic synthetic acaricides in indoor environments justify further studies on A. heterotropoides root extract and steam distillate preparations containing the active constituents described as potential contact-action fumigants for the control of mites.

Comparative analysis of two species of Asari Radix et Rhizoma by electronic nose, headspace GC-MS and chemometrics.[Pubmed:23973758]

J Pharm Biomed Anal. 2013 Nov;85:231-8.

Traditional Chinese medicines (TCM) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. In this paper, electronic nose, headspace gas chromatography-mass spectrometry (GC-MS) and chemometrics methods were applied to differentiate two species of Asari Radix et Rhizoma by their odors. The samples used were the dried roots and rhizomes of Asarum heterotropoides var. mandshuricum (AH) and Asarum sieboldii (AS). The electronic nose was used to determine the odors of the samples and enabled rapid differentiation of AH and AS when coupled with principal component analysis. Headspace GC-MS was utilized to reveal the differences between the volatile constituents of AH and AS. In all, 54 volatile constituents were identified, and 9 major constituents (eucalyptol, eucarvone, 3,5-dimethoxytoluene, 3,4,5-Trimethoxytoluene, methyleugenol, 2,3,5-trimethoxytoluene, croweacin, pentadecane and asaricin) could be used as chemical markers to distinguish these two species. AH contained higher relative contents of eucarvone (1.79-16.76%), 3,5-dimethoxytoluene (6.64-26.52%), 3,4,5-Trimethoxytoluene/methyleugenol (6.43-31.67%) and 2,3,5-trimethoxytoluene (1.64-6.66%), whereas AS had higher relative contents of eucalyptol (14.06-24.95%), croweacin (5.64-13.55%), pentadecane (8.44-20.82%) and asaricin (7.03-13.45%). Moreover, AH and AS could be distinguished according to the contents of either all 54 identified volatile constituents or only the 9 major constituents by employing cluster analysis. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two species of Asari Radix et Rhizoma by their odors.

Constituents of Asarum sieboldii with inhibitory activity on lipopolysaccharide (LPS)-induced NO production in BV-2 microglial cells.[Pubmed:18293448]

Chem Biodivers. 2008 Feb;5(2):346-51.

Bioassay-guided fractionation of the root extract of Asarum sieboldii led to the isolation of the four active compounds (-)-sesamin (1), (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), kakuol (3), and '3,4,5-Trimethoxytoluene' (=1,2,3-trimethoxy-5-methylbenzene; 4), in terms of inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compounds 1-4 showed potent inhibition of NO production, with IC(50) values in the low nanomolar-to-micromolar range. Also isolated were the known compounds methylkakuol (5), '3,5-dimethoxytoluene', safrole, asaricin, methyleugenol, and (-)-asarinin, which were found to be inactive in the above assay. Among the ten known isolates, compounds 1, 2, and 5 were found for the first time in this plant.

Aqueous chlorination of the antibacterial agent trimethoprim: reaction kinetics and pathways.[Pubmed:17173950]

Water Res. 2007 Feb;41(3):647-55.

Trimethoprim (TMP), one of the antibacterials most frequently detected in municipal wastewaters and surface waters, reacts readily with free available chlorine (i.e., HOCl) at pH values between 3 and 9 (e.g., the pH-dependent apparent second-order rate constant, k''(app)=5.6 x 10(1)M(-1)s(-1), at pH 7). Solution pH significantly affects the rate of TMP reaction with HOCl. The reaction kinetics in reagent water systems can be well described by a second-order kinetic model incorporating speciation of both reactants and accounting for acid-mediated halogenation of TMP's 3,4,5-trimethoxybenzyl moiety. Studies with the substructure model compounds 2,4-diamino-5-methylpyrimidine and 3,4,5-Trimethoxytoluene show that TMP reacts with HOCl primarily via its 3,4,5-trimethoxybenzyl moiety at acidic pH, and with its 2,4-diaminopyrimidinyl moiety at circumneutral and alkaline pH. LC/MS product analyses indicate that the TMP structure is not substantially degraded upon reactions with HOCl. Instead, a wide variety of (multi)chlorinated and hydroxylated products are formed. Experiments with real drinking water and wastewater matrixes confirmed that substantial TMP transformation can be expected for conditions typical of wastewater and drinking water chlorination.