As part of a program aiming at the selection of yeast strains which might be of interest as sources of natural flavors and fragrances, the bioreduction of (4R)-(-)-carvone and (1R)-(-)-myrtenal by whole-cells of non-conventional yeasts (NCYs) belonging to the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Kazachstania, Kluyveromyces, Lindnera, Nakaseomyces, Vanderwaltozyma, and Wickerhamomyces was studied. Volatiles produced were sampled by means of headspace solid-phase microextraction (SPME) and the compounds were analyzed and identified by gas chromatography-mass spectroscopy (GC-MS). Yields (expressed as % of biotransformation) varied in dependence of the strain. The reduction of both (4R)-(-)-carvone and (1R)-(-)-myrtenal were catalyzed by some ene-reductases (ERs) and/or carbonyl reductases (CRs), which determined the formation of (1R,4R)-dihydrocarvone and (1R)-myrtenol respectively, as main flavoring products. The potential of NCYs as novel whole-cell biocatalysts for selective biotransformation of electron-poor alkenes for producing flavors and fragrances of industrial interest is discussed.
来源:Hazardous Substances Data Bank (HSDB)
代谢
... 酮类（例如，香芹酮和薄荷酮）被还原为二级醇，然后这些二级醇以葡萄糖苷酸的形式被排出体外。
... Ketones (e.g., carvone and menthone) are reduced to secondary alcohols which are then excreted as glucuronides.
The cyclic monoterpene ketone (-)-carvone was metabolized by the plant pathogenic fungus Absidia glauca. After 4 days of incubation, the diol 10-hydroxy-(+)-neodihydrocarveol was formed. The absolute configuration and structure of the crystalline substance was identified by means of X-ray diffraction and by spectroscopic techniques (MS, IR, and NMR). The antimicrobial activity of the substrate and metabolite was assayed with human pathogenic microorganisms.
D-Carvone toxicokinetics in humans features rapid elimination with a half life of 2.4 hours, no data are available for L-carvone. No toxicokinetic data on carvone in animals are available. The evidence from in vivo, in vitro, and in silico assessments has shown that carvone metabolism is likely to be different in humans and rats - with further possible differences between metabolism in male and female rats. It is also evident that when compared with carvone itself, the metabolites are not likely to be different in terms of GI uptake or half-life in the body. Toxicokinetic data on other monoterpenes in the rat such as menthol suggest that metabolism involves conjugation to a glucuronide for which enterohepatic recirculation occurs in the rat but not in humans. Considering the molecular weight of glucuronidated carvone metabolites, they may undergo enterohepatic recirculation in rats but not in humans, making the rat more sensitive than humans for these compounds. /D-Carvone and L-Carvone/
In vivo metabolism of D- and L-carvone has been investigated in six human volunteers (three males, three females) after oral dosing (1 mg/kg bw), with collection of urine samples 24 hr before and after the ingestion of each enantiomer separately. Chemical structures of the metabolites were elucidated using mass spectral analysis in combination with metabolite syntheses and NMR analysis. For this, the urinary samples were treated with sulphatase and glucuronidase, assuming conjugation of phase I metabolites. However, no quantitative data on excretion of conjugated forms of the metabolites were reported. The study identified three side-chain oxidation products as the main primary unconjugated metabolites of D- and L-carvone: dihydrocarvonic acid, carvonic acid, and uroterpenolone, with 10-hydroxycarvone as the proposed intermediate metabolic step. However, unlike other species, the presence of 10-hydroxycarvone was not detected in humans and /it was/ suggested this was due to more efficient oxidation of 10-hydroxycarvone leading to carvonic acid. According to /the study/, there were no differences in the metabolism of D- and L-carvone. However, the results presented only refer to "after carvone ingestion", although apparently both carvone enantiomers were ingested by the volunteers in independent trials. According to the author, all metabolites were identical after the application of either D- or L-carvone. However, the configurations of metabolites were not identified and the chromatographic analyses were only performed on a nonchiral stationary phase. This experimental set-up does not allow differentiation of the stereospecific metabolism of D- and L-carvone. /D-Carvone and L-Carvone/
IDENTIFICATION AND USE: Carvone is a pale-yellowish or colorless liquid. The following uses have been identified for carvone: pesticide, feed additive, veterinary medicine use, flavoring substance and natural food occurrence, personal care products: D- and L-carvone are used in a variety of non-food consumer products, including cosmetics and personal care products. Some of these, such as toothpaste and mouthwash may result in oral intake of carvone. It is also used as natural insect repellent. HUMAN EXPOSURE AND TOXICITY: The sensitizing potential of l-carvone has been considered low, but it has occasionally caused contact allergy in users of spearmint toothpaste and chewing gum. L-Carvone inhibited proliferation of MCF 7 and MDA MB 231 cells and inhibited the migration of breast cancer cell lines. L-carvone induced apoptosis as observed by nuclei fragmentation and the presence of apoptotic bodies in DAPI, AnnexinV/propidium iodide, and TUNEL assays. l-carvone exposure arrested MCF 7 cells in S phase of the cell cycle. DNA damage caused by L-carvone was apparent from the increased tail moment in comet assay, which could be induced by an increase in ROS that was measured using a fluorescence probe. ANIMAL STUDIES: Clinical signs after acute exposure in mice and rats were different depending on the route of exposure. After acute oral administration, these included hunched posture and lethargy and occasional body tremor with no abnormalities at necropsy. After acute dermal exposure no systemic or skin effects were observed whereas after inhalation of carvone, respiratory effects were noted as well as alopecia and impairment of body weight gain. Carvone caused transient depression of central nervous system activity in mice. In developmental study rats were given 0, 3, 10 or 30 mg/kg/day of D-carvone (95%) for 10 weeks prior to mating until termination. There were no differences between treated and control animals in any of the indices of reproductive performance or in the results of the sperm morphology and motility measurements. Males of the F0 generation given 30 mg/kg bw/day had increased relative kidney weights. Histopathology of the male kidneys showed changes typical of alpha2u-globulin nephropathy at all doses. No other histopathological changes were reported and no similar changes were observed in females. Males of the F1 generation given 30 and 90 mg/kg bw/day had increased mean relative liver and kidney weights. Histopathology of the male kidneys showed changes typical of alpha2u-globulin nephropathy at all doses. No differences were seen in females and no other histopathological changes were reported. Carvone showed equivocal results for mutagenicity in a sister chromatid exchange study and a chromosomal aberration study with Chinese hamster ovary cells. Results from an in vivo UDS assay in liver and an in vivo micronucleus test were negative while those of an in vitro test for chromosome aberrations were not clear-cut. It was concluded that carvone should not be considered genotoxic. Groups of 50 male and 50 female mice were administered 0, 375, or 750 mg/kg D-carvone in corn oil by gavage, 5 days/wk for 103 weeks. Under the conditions of these two yr gavage studies, there was no evidence for the carcinogenic activity of D-carvone for male or female mice.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
神经毒素 - 急性溶剂综合征
Neurotoxin - Acute solvent syndrome
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
The objective was to investigate the difference in penetration enhancing effect of R-carvone, S-carvone and RS-carvone on the in vitro transdermal drug permeation. In vitro permeation studies were carried out across neonatal rat epidermis from 2% w/v HPMC (hydroxypropyl methylcellulose) gel containing 4% w/v of nicorandil (a model drug) and a selected concentration (12% w/v) of either R-carvone, S-carvone, or RS-carvone against a control. The stratum corneum (SC) of rats was treated with vehicle (70 %v/v ethanol-water) or ethanolic solutions of 12% w/v R-carvone, S-carvone or RS-carvone. The enhancement ratio (ER) of R-carvone, S-carvone, and RS-carvone when compared to control was about 37.1, 31.2, and 29.9, respectively, indicating enantioselective penetration enhancing effect of carvone enantiomers. Furthermore, there was a significant decrease in the lag time required to produce a steady-state flux of nicorandil with S-carvone when compared to R-carvone and RS-carvone. DSC and FT-IR studies indicate that the investigated enantiomers of carvone exhibit a difference in their ability to affect the cellular organization of SC lipids and proteins thereby showing enantioselective transdermal drug permeation. It was concluded that R-carvone exhibited a higher penetration enhancing activity on transdermal permeation of nicorandil when compared to its S-isomer or racemic mixture.
Naturally occurring compounds belonging to the two chemical groups were studies for their capacities to inhibit N-nitrosodiethylamine-induced carcinogenesis in female A/J mice. One group consists of organosulfur compounds found in Allium species, including garlic, onions, leeks, and shallots, and the other, two monoterpenes, i.e., D-limonene and D-carvone. In these experiments D-limonene and D-carvone were tested and reduced forestomach tumor formation by slightly over 60% and pulmonary adenoma formation by about 35%. The results of these studies provide evidence of an increasing diversity of naturally occurring compounds having the capacity to inhibit nitrosamine carcinogenesis.
Carvone is a monoterpene that is present in spearmint (Mentha spicata) and caraway (Carum carvi) essential oils and has been shown to have anticonvulsant effects, likely through the blockade of voltage-gated sodium channels, and anxiolytic-like effects. Considering that some anticonvulsants that blocked voltage-gated sodium channels (e.g., sodium valproate and carbamazepine) exert clinical antimanic effects, the aim of the present study was to evaluate (R)-(-)-carvone and (S)-(+)-carvone in animal models of mania (i.e., hyperlocomotion induced by methylphenidate and sleep deprivation). Mice that were treated with methylphenidate (5 mg/kg) or sleep-deprived for 24 hr using a multiple-platform protocol exhibited an increase in locomotor activity in an automated activity box. This effect was blocked by pretreatment with acute (R)-(-)-carvone (50-100 mg/kg), (S)-(+)-carvone (50-100 mg/kg), and lithium (100 mg/kg, positive control). These doses did not alter spontaneous locomotor activity in the methylphenidate-induced experiments while (S)-(+)-carvone decreased spontaneous locomotor activity in sleep deprivation experiment, indicating a sedative effect. Chronic 21-day treatment with (R)-(-)-carvone (100 mg/kg), (S)-(+)-carvone (100 mg/kg), and lithium also prevented methylphenidate-induced hyperactivity. The present results suggest that carvone may have an antimanic-like effect.
In humans, D-carvone pharmacokinetics was investigated in 15 male volunteers who, after a 10 hr fast, took 5 capsules of an immediate release formulation containing 20 mg caraway oil. Carvone concentrations in plasma were determined by GC/MS, with a limit of quantification of 0.5 ng/mL for carvone. Pharmacokinetic parameters were determined, i.e., area-under the plasma-concentration curve (AUC) of 28.9+/- 20.0 ng.mL/hr , plasma peak concentration (Cmax) of 14.8+/-10.4 ng/mL with a time to reach Cmax (Tmax) of 1.3 hours and a half life of 2.4 hours. Inter-individual differences determined as the coefficients of variation in AUC, Cmax, and t1/2 were 69%, 74%, and 50% respectively. /D-Carvone/
[EN] SUBSTITUTED QUINAZOLINES AS FUNGICIDES<br/>[FR] QUINAZOLINES SUBSTITUÉES, UTILISÉES EN TANT QUE FONGICIDES
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2010136475A1
公开（公告）日：2010-12-02
The present invention relates to a compound of formula (I) wherein wherein the substituents have the definitions as defined in claim 1or a salt or a N-oxide thereof, their use and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.
式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
Thieno-pyrimidine compounds having fungicidal activity
申请人：Brewster Kirkland William
公开号：US20070093498A1
公开（公告）日：2007-04-26
The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.
本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。
[EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2013079350A1
公开（公告）日：2013-06-06
Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.
式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
THIENYLPYRIDYLCARBOXAMIDES
申请人：Dunkel Ralf
公开号：US20110105564A1
公开（公告）日：2011-05-05
Novel thienylpyridylcarboxamides of the formula (I)
The present application is also directed to a plurality of processes for preparing these compounds and their use for controlling unwanted microorganisms, and also novel intermediates and their preparation.
