Identification of oxidation products of (-)-epigallocatechin gallate and (-)-epigallocatechin with H(2)O(2)

(-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are two important antioxidants in tea. They also display some antitumor activities, and these activities are believed to be mainly due to their antioxidative effects. However, the specific mechanisms of antioxidant action of tea catechins remain unclear. In this study are isolated and identified two novel reaction products of EGCG and one product of EGC when they were reacted separately with H(2)O(2). These products are formed by the oxidation and decarboxylation of the A ring in the catechin molecule. This study provides unequivocal proof that the A ring of EGCG and EGC may also be an antioxidant site. This study also indicates an additional reaction pathway for the oxidation chemistry of tea catechins.     

The formation of 2-chlorobenzamide upon hydrolysis of the benzoylphenylurea insecticide 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea in different water systems

It has been reported that 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea (CCU), an insect growth regulator, has no measurable toxicity to nontarget organisms and is essentially harmless to humans. However, one of its degradation products, 2-chlorobenzamide (CBA), is suspected of being a carcinogen. Therefore, the maximum concentration of CBA formed and the dynamics of its formation need to be given careful attention after CCU is used in the field. This paper describes the degradation of CCU to form CBA in three different water systems (distilled water, spring water, and simulated seawater) and the effects of temperature on the dynamics of CBA formation. The results indicate that the maximum level of CBA concentration is different in the different systems (highest in spring water) and that the temperature has a significant impact on the process (higher temperature leads to higher and earlier peak of CBA concentration). The maximum concentration of CBA after application of CCU was approximately 3.8% of the initial concentration of CCU at 35 degrees C in distilled water, and 2.4% in spring water at 25 degrees C.     

Photodegradation of 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea in different media and toxicity of its reaction products

The photodegradation of 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea in simulated air, methanol, dioxane, hexane, and water, with a xenon lamp as light source, was studied. The rate constants and half-lives of this compound in various media under nitrogen or oxygen were determined. The photoreaction products were analyzed with HPLC-UV, GC-MS, and direct probe MS and found to have some differences in different cases. With (32)P postlabeling DNA adduct formation experiments, one of the main products, 2-chorobenzamide, was found to be able to form a DNA adduct.     

N-Nitrosation of myosmine yields HPB (4-hydroxy-1-(3-pyridyl)-1-butanone) and NNN (N-nitrosonornicotine)

N-Nitrosonornicotine (NNN) is formed by synthetic or biological N-nitrosation of the tobacco alkaloid nornicotine. Following metabolic activation of NNN, DNA and protein adducts are formed releasing 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), an actual biomarker to differentiate between tobacco smokers and passive smokers. NNN and HPB can be prepared in a new one-step reaction by N-nitrosation of the nicotinoid myosmine which has been found not only in tobacco but also in nut products. The reaction was tested also in human gastric juice. The formation rate of NNN and HPB depends on the pH value in the reaction solutions. This is important under the aspect of myosmine uptake by humans from other biological sources and subsequent biological activation. The new reaction pathway indicates that human exposure to nicotinoid nitrosation products seems to be not restricted exclusively to tobacco.     

Calculation of the peak concentration of 2-chlorobenzamide generated in the hydrolysis of the benzoylphenylurea insecticide 1-(2-chlorobenzoyl)-3-(4-chlorophenyl)urea

1-(2-chlorobenzoyl)-3-(4-chlorophenyl)urea (CCU), a new analogue of diflubenuron and PH-6038, has been widely used in agriculture and forestry as a molt-inhibiting hormone insecticide which was developed in China. 2-Chlorobenzamide, a main degradation product of CCU in the environment, has been identified as a potential carcinogen, so the content of 2-chlorobenzamide from the breakup of CCU will directly affect the environmental safety of CCU. In this paper we describe a simple, rapid, and convenient prediction model for predicting the level and time of occurrence of the peak concentration of 2-chlorobenzamide in the hydrolysis of CCU verified by experimental data. The time for reaching the peak concentration of 2-chlorobenzamide (tm) at 25 degrees C and pH 6 is 13.5 d, and the maximum concentration of 2-chlorobenzamide (ym) is 3.2% of the initial concentration of CCU according to the results from the prediction model. These results are similar to the real values from the experiments, which are 22 d and 1.6% of the initial concentration of CCU, respectively. The difference between the values of the prediction and experiment is discussed, and it is demonstrated that the predicting model is highly credible.     

Metabolism of N-[(R)-1-(2,4-dichlorophenyl)ethyl]-2-cyano-3,3-dimethylbutanamide (Delaus, S-2900) and its isomer, N-[(S)-1-(2,4-dichlorophenyl)ethyl]-2-cyano-3,3-dimethylbutanamide (S-2900S), in rats. 1. Identification of metabolites in feces and urine

Rats were orally dosed with a 1:1 diastereomixture of N-[(R)-1-(2,4-dichlorophenyl)ethyl]-2-cyano-3,3-dimethylbutanamide (Delaus, S-2900) and N-[(S)-1-(2,4-dichlorophenyl)ethyl]-2-cyano-3,3-dimethylbutanamide (S-2900S), both labeled with 14C, at 200 mg/kg/day for 5 consecutive days, and 16 metabolites in urine and feces were purified by a combination of several chromatographic techniques. The chemical structures of all isolated metabolites were identified by spectroanalyses (NMR and MS). Several of them were unique decyanated and/or cyclic compounds (lactone, imide, cyclic amide, cyclic imino ether forms). Major biotransformation reactions of the mixture of S-2900 and S-2900S in rats are proposed on the basis of the metabolites identified in this study.     

Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4- (2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (S-53482) in rat. 1. Identification of a sulfonic acid type conjugate

To examine the metabolic fate of 7-fluoro-6-(3,4,5, 6-tetrahydrophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3( 4H)-one (S-53482), rats were given a single oral dose of [phenyl-(14)C]-S-53482 at 1 (low) or 100 (high) mg/kg. The radiocarbon was almost completely eliminated within 7 days after administration in both groups. (14)C recoveries (expressed as percentages relative to the dosed (14)C) in feces and urine were 56-72 and 31-43%, respectively, for the low dose and 78-85 and 13-23%, respectively, for the high dose. S-53482 and seven metabolites were identified in urine and feces. Six of them were purified by several chromatographic techniques and identified by spectroanalyses (NMR and MS). Alcohol derivatives and an acetoanilide derivative were isolated from urine. Three sulfonic acid conjugates having a sulfonic acid group incorporated into the double bond of the 3,4,5,6-tetrahydrophthalimide moiety were isolated from feces. On the basis of the metabolites identified in this study, the metabolic pathways of S-53482 in rats are proposed.     

2-(1H-pyrrolyl)carboxylic acids as pigment precursors in garlic greening

Six model compounds having a 2-(1 H-pyrrolyl)carboxylic acid moiety and a hydrophobic R group were synthesized to study their effects on garlic greening, the structures of which are similar to that of 2-(3,4-dimethyl-1 H-pyrrolyl)-3-methylbutanoic acid (PP-Val) (a possible pigment precursor for garlic greening). The puree of freshly harvested garlic bulbs turned green after being soaked in solutions of all these compounds, and with both increasing concentrations and incubation time the green color of the puree became deeper. In contrast, neither pyrrole alone nor pyrrole combined with free amino acids had the ability to discolor the puree. The compounds exhibited a good relationship between structure and activity of garlic greening, namely, the smaller the size of the R group, the larger the contribution. Also, it was found that the unidentified yellow species can be produced by reacting the model compounds with pyruvic acid at room temperature (23-25 degrees C). Moreover, blue species were formed by incubation of the model compounds with di(2-propenyl) thiosulfinate at room temperature. On the basis of these observations, a pathway for garlic greening was proposed.     

Synthesis and antifungal activity of a series of N-substituted [2-(2,4-dichlorophenyl)-3-(1,2,4-triazol-1-yl)]propylamines

A series of N-mono- or N, N-disubstituted [2-(2,4-dichlorophenyl-3-(1,2,4-triazol-1-yl)]propylamines and N-[2-(2,4-dichlorophenyl-3-(1,2,4-triazol-1-yl)propyl]amides were synthesized and tested for their fungicidal activity in vitro and in vivo against a group of plant pathogenic fungi. Some compounds exhibited a fairly good in vitro activity. The replacement of the ether group of tetraconazole with a secondary or tertiary amino group leads to compounds that maintain the antifungal activity on several phytopathogenic fungi, provided that the substituents are not too bulky or lipophilic. The allyl, propargyl, and cyclopropyl groups appear particularly suitable. Although these compounds have some structural similarities with terbinafine and naftifine, which act as squalene epoxidase inhibitors, they maintain the usual mechanism of action of the other triazoles.     

Liquid chromatographic determination of 2-(2-quinolinyl)-1H-indene-1,3-[2H]-dione and other organic-soluble matter in D&C Yellow No. 10

A sensitive, reproducible method that uses an Extrelut QE column and liquid chromatography (LC) in the reverse phase mode is described for the determination of 2-(2-quinolinyl)-1H-indene-1,3-[2H]-dione and other organic-soluble matter found in D&C Yellow No. 10. With this method the organic-soluble matter is extracted from D&C Yellow No. 10 on an Extrelut QE column, and the extract is concentrated and analyzed by LC. Recoveries averaged 104% for 2-(2-quinolinyl)-1H-indene-1,3-[2H]-dione added to purified D&C Yellow No. 10 at levels ranging from 0.50 to 5.96 ppm.     

(E)-1-(2,3,6-trimethylphenyl)buta-1,3-diene: a potent grape-derived odorant in wine

(E)-1-(2,3,6-Trimethylphenyl)buta-1,3-diene (TPB) was identified as a potent odorant in acid hydrolysates of crude glycoconjugate fractions isolated from grapes and grape vine leaves. TPB was also identified in a Semillon wine, using gas chromatography/mass spectrometry, by co-injection with an authentic sample. TPB had an aroma detection threshold of 40 ng/L in a neutral white wine and the concentration of TPB in four out of five white wines analyzed ranged from 50 to 210 ng/L.     

Generation of (E)-1-(2,3,6-trimethylphenyl)buta-1,3-diene from C13-norisoprenoid precursors

Three C(13)-norisoprenoid compounds, 3,6,9-trihydroxymegastigma-4,7-diene (6), 3,4,9-trihydroxymegastigma-5,7-diene (4), and the actinidols (8), have all been synthesized and subjected to acid hydrolysis. All three were shown to generate (E)-1-(2,3,6-trimethylphenyl)buta-1,3-diene (1) under wine conservation conditions. At 45 degrees C, approximately 4000-5000 ng/L of 1 was formed from 1.0 mg/L of precursor, after 173 days, while at 25 degrees C more wine-like amounts (200-600 ng/L) were observed. A glucoside, 4,5-dihydrovomifoliol-C(9)-beta-d-glucopyranoside (9b), was isolated from grapevine leaves by multilayer coil countercurrent chromatography (MLCCC), and its stereochemistry was deduced as being (5R, 6S, 9R) by NMR and CD spectroscopy. Hydrolysis of this glucoside produced 1, but in quantities insufficient to account for the levels observed in wine.