Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “KETONES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1997

Electron-Transfer Reactions of Aromatic alpha,beta-Epoxy Ketones: Factors That Govern Selective Conversion to beta-Diketones and beta-Hydroxy Ketones.

Photoreaction of trans-1-(4-cyanophenyl)-3-phenyl-2,3-epoxy-1-propanone (trans-4'-cyanochalcone epoxide) with various electron donors was studied. Irradiation of this epoxy ketone with amines produced 1-(4-cyanophenyl)-3-phenyl-1,3-propanedione and 1-(4-cyanophenyl)-3-hydroxy-3-phenyl-1-propanone in various ratios depending on the kinds of amine and solvent used. A reaction mechanism involving an amine cation radical-assisted rearrangement of the epoxy ketone anion radical was proposed to be most consistent with the marked change in the yield of beta-diketone. On the other hand, the timing of proton transfer to the anionic intermediates is considered to be a key factor to yield the beta-hydroxy ketone. Information obtained from the photochemical study was useful to find the reaction conditions for the conversion of several aromatic epoxy ketones to hydroxy ketones by the use of samarium diiodide. Addition of methanol significantly changed the product distribution. Proper choice of water or methanol as a proton source produced hydroxy ketones in moderate to good yields.

Journal Article↗
PubMed2002

Methyl isobutyl ketone and methyl ethyl ketone in urine as biological markers of occupational exposure to these solvents at low levels.

OBJECTIVE: To examine whether unmetabolized methyl isobutyl ketone in urine is a useful marker of low-level occupational exposure to this ketone solvent, as is the case for methyl ethyl ketone. METHODS: The study was conducted in the second half of a working week. In total, 27 furniture-making workers (19 men and eight women) and 11 non-exposed controls (six men and five women) volunteered to participate in the study. Time-weighted average (TWA; 8-h) concentration of vapors of several solvents in air, including methyl isobutyl ketone (MIBK-A) and methyl ethyl ketone (MEK-A) was monitored by diffusive sampling. Urine samples collected at the end of the shift were subjected to head-space gas chromatography (GC) analysis for the unmetabolized solvents (i.e., MIBK-U and MEK-U). The relationship between the concentration of the solvent vapor and the corresponding solvent level in urine was examined by simple as well as multiple regression analysis. RESULTS: The exposures to MIBK and MEK were well below the current occupational exposure limit levels, but the maximum levels of exposure to toluene and ethylbenzene were around the corresponding exposure limit. The correlation of the TWA concentration of the solvent in air with the concentration of the corresponding solvent in the end-of-shift urine sample was significant both for MIBK and for MEK, and the correlation coefficient was larger for MIBK than for MEK. The slope in the exposure-excretion regression line was almost twice as steep for MEK than for MIBK, possibly due to the difference in water solubility. Approximately 0.12% of MIBK absorbed in the lungs will be excreted into urine, whereas the yield for MEK was somewhat higher (0.19%). CONCLUSION: MIBK in urine is a good marker of exposure to MIBK, as in the case of MEK in urine for MEK exposure.

Adult↗
PubMed1992

Comparative behaviour of calpain and cathepsin B toward peptidyl acyloxymethyl ketones, sulphonium methyl ketones and other potential inhibitors of cysteine proteinases.

Peptidyl acyloxymethyl ketones, previously established as potent inactivators of the lysosomal cysteine proteinase cathepsin B, were evaluated against smooth-muscle calpain, a member of the family of Ca(2+)-dependent cysteine proteinases. Only modest rates of time-dependent inhibition could be achieved, even with peptidyl affinity groups optimized for calpain and linked to a carboxylate leaving group of very low pKa [2,6-(CF3)2PhCOO-, pKa 0.58]. Selective inactivation of cathespin B versus calpain was consistently observed with this type of inhibitor. Examination of other potential inhibitors revealed a rank order of potency against calpain to be: peptidyl sulphonium methyl ketones > fluoromethyl ketones, diazomethyl ketones >> acyloxymethyl ketones, an order which differs sharply from that found for cathespin B.

Amino Acid Sequence↗
PubMed1991

Increase of urinary ketone body excretion in selenium-deficient rats is a ketone-specific change.

The effects of selenium (Se) deficiency on urinary ketone body excretion in starved rats were examined. Rats were fed a basal diet which was Se-deficient (Se content: 0.011 micrograms/g) or a Se-adequate diet (the basal diet supplemented with 0.1 micrograms Se/g as sodium selenite). On the 11th and 22nd week of the feeding period, Se-deficient status in rats fed the basal diet was verified by the observation that the Se content and glutathione peroxidase activity in their plasma, erythrocytes, and livers were markedly lowered. On the 4th, 6th, 11th, 15th, and 22nd week, the rats were starved for 48 h and the urinary excretion of ketone bodies (acetoacetate (AcAc) and 3-hydroxybutyrate (3-OHBA)), urea, and creatinine were examined. The urinary excretion of AcAc and 3-OHBA during the second 24 h of the 48-h starvation period were markedly higher in the Se-deficient rats than in the Se-adequate rats for all weeks examined, while the urine volume and the excretion of urea and creatinine were similar in the Se-deficient and Se-adequate rats, irrespective of the feeding period and the number of hours of starvation. On the 22nd week, the plasma ketone body levels were also determined and significantly higher plasma 3-OHBA levels were observed in the Se-deficient rats than in the Se-adequate rats 72 h after starvation began. These results indicate that Se deficiency causes an increase of urinary ketone body excretion in starved rats and that the increase is ketone-specific with no changes in major urinary profiles.

3-Hydroxybutyric Acid↗
PubMed1980

Anti-inflammatory activity of diazomethyl ketone and chloromethyl ketone analogs prepared from N-tosyl amino acids.

A series of diazomethyl ketone and chloromethyl ketone analogs prepared from N-tosyl amino acids was shown to have anti-inflammatory activity in mice at 20 mg/kg and in rats at 10 mg/kg. N-Tosyl-L-alanine and N-tosyl-beta-alanine chloromethyl ketones demonstrated the most potent anti-inflammatory activity. The writhing reflex also was inhibited at 20 mg/kg in mice. In the tail flick test, N-tosyl-D,L-alanine and N-tosyl-D,L-isoleucine chloromethyl ketones demonstrated the highest increase in time. Toxicity studies indicated good therapeutic indexes for most of these agents.

Amino Acids↗
PubMed1995

Tissue concentrations of methyl isobutyl ketone, methyl n-butyl ketone and their metabolites after oral or inhalation exposure.

Quantitative relationships between plasma, liver and lung methyl isobutyl ketone (MiBK) and methyl n-butyl ketone (MnBK) concentrations after oral or inhalation exposure were established. Their respective metabolites (4-methyl-2-pentanol, 4-hydroxy-methyl isobutyl ketone, 2-hexanol, and 2,5-hexanedione) were also quantified. Male Sprague-Dawley rats were exposed for 3 days to MiBK or MnBK vapors (4 h/day) or treated orally for 3 days with a MiBK- or MnBK-corn oil solution. Both ketones and their respective metabolites in plasma or tissue concentrations were determined by gas chromatography. MiBK and MnBK plasma and tissue concentrations increased in a dose-related manner with the administered dose irrespective of the route of administration. Metabolite concentrations, however, were influenced by the route of administration.

Administration, Inhalation↗
PubMed2000

Heavy ketones, the heavier element congeners of a ketone.

In contrast to ketones, one of the most important classes of organic compounds, their heavier element congeners, "heavy ketones", are much less explored because of their extremely high reactivities. This Account reviews the synthesis, reactivities, and structures of stable heavy ketones containing silicon, germanium, and tin as well as those of moderately stable lead analogues. These heavy ketones are kinetically stabilized by taking advantage of bulky substituents, yet they can undergo a variety of reactions due to the intrinsic high reactivity of heavier group 14-16 double bonds. Systematic comparisons for silicon through lead compounds reveal interesting differences in their properties, depending on the elements.

Crystallography, X-Ray↗
PubMed2001

Facile approach to enantiomerically pure alpha-amino ketones by Friedel-Crafts aminoacylation and their conversion into peptidyl ketones.

In this article we describe a versatile and straightforward preparative approach to chiral aryl alpha-amino ketones via a Friedel-Crafts-type reaction of stable and enantiomerically pure N-Fmoc protected L-amino acid chlorides with toluene in the presence of aluminum trichloride. The developed methodology provided aryl alpha-amino-p-methylphenyl ketones, which can be obtained and isolated as free bases or recovered as their N-acetyl derivatives, after treatment with acetic anhydride in chloroform at room temperature, subsequent to the Lewis acid induced removal of the 9-fluorenylmethoxycarbonyl protecting group. The Friedel-Crafts-like process and the cleavage of the amino function masking group can selectively be performed since, as verified in all cases, the alpha-aminoacylation step occurred with kinetics that were faster than those required to remove the N-protection. The presented approach was also explored as a facile and useful synthetic tool for the preparation of optically pure ketone di- and tripeptides. These compounds can be obtained in exceptionally overall yields without need of chromatographic purification. Moreover, either aryl alpha-amino ketones or modified di- and tripeptides, in all cases, can be isolated in very high chemical and optical purity without recourse to resolution of diastereomeric mixtures, since the chiralities of the asymmetric amino acid educts were completely conserved throughout the entire process.

Dipeptides↗
PubMed2002

An NMR method for assigning relative stereochemistry to beta-hydroxy ketones deriving from aldol reactions of methyl ketones.

We describe a simple 1H NMR analysis that permits the stereochemistry of beta-hydroxy ketones to be assigned by visual inspection of the ABX patterns for the alpha-methylene unit of the beta-hydroxy ketone in the 1H NMR spectra. This method has been verified by application to a wide range of beta-hydroxy ketones deriving from aldol reactions of chiral aldehydes with a variety of chiral and achiral methyl ketone enolates (see Tables 1 and 2). The stereochemistry of 54 of these compounds have been assigned by rigorous chemical methods.

Catalysis↗
PubMed1996

Ketone potentiation of haloalkane-induced hepatotoxicity: CCl4 and ketone treatment on hepatic membrane integrity.

Previous results in male Sprague-Dawley rats indicate that acetone (A), methyl ethyl ketone (MEK), and methyl isobutyl ketone (MiBK) pretreatments (3 d, p.o.) at a dosage of 6.8 mmol/kg potentiate CCl4 hepatotoxicity. The potentiation potency profile observed was MiBK > A > MEK. In the present study, male Sprague-Dawley rats were treated for 3 d with 6.8 mmol/kg (p.o.) of A, MEK, or MiBK using Emulphor as vehicle (10 ml/kg). Rats were either killed 18 h after the last pretreatment or treated with CCl4 (prepared in corn oil) and then killed 48 h later. Livers were perfused; purified plasma membrane (PM), sinusoidal (SM) and basal canalicular membrane (BCM) fractions were prepared. Membrane fluidity was monitored by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). The following membrane enzymes were measured to monitor membrane purity and treatment effects: 5'-nucleotidase (5N), leucine aminopeptidase (LAP), and alkaline phosphatase (AP). Our results suggest that CCl4 modifies membrane integrity as indicated by a decrease in liver membrane 5N, LAP, and AP activity. CCl4 also increased the fluidity of the lipid and protein portions of the liver membranes as measured by the DPH and TMA-DPH fluorescence probes, respectively. Of the three ketones, only A altered CCl4 effects on plasma membrane enzymes and decreased BCM fluidity. The data only partially support increased susceptibility of liver membranes by ketone pretreatment as a factor implicated in the mechanism of potentiation of CCl4-induced hepatotoxicity.

5'-Nucleotidase↗
PubMed1985

Stereoselective hydrolysis of 16 alpha-halo-17-keto steroids and long-range substitution effects on the hydrolysis of 16 alpha-bromo-17-ketones and 2 alpha-bromo-3-ketones.

Epimerizations of 16 alpha-chloro- (1a), bromo- (1b), and iodo-3 beta-hydroxy-5-androsten-17-one (1c) by a brief treatment with 0.2 equiv NaOH in aqueous pyridine reached equilibrium between 16 alpha- and 16 beta-halo ketones. 16 alpha-/16 beta-Halo ketone ratios at equilibrium were 1.5 for Cl, 1.25 for Br, and 1.0 for I. Kinetic analysis showed that compounds 1a-c were stereoselectively converted to the corresponding 16 alpha-hydroxy derivative 3 by an SN2 mechanism, in which the order of the apparent reactivity was Br greater than I greater than Cl. The hydrolysis of a number of 16 alpha-bromo-17-ketones and 2 alpha-bromo-3-ketones was carried out. The yields of the corresponding alcohols were found to depend on remote structural features in the steroids.

17-Ketosteroids↗
PubMed2005

A novel pyrrolidine imide catalyzed direct formation of alpha,beta-unsaturated ketones from unmodified ketones and aldehydes.

A method for direct, stereoselective preparation of (E)-alpha,beta-unsaturated ketones from ketones and aldehydes, promoted by a novel pyrrolidine imide organocatalyst, has been developed in moderate to high yields. Unlike the Claisen-Schmidt condensation and Lewis acid catalyzed tandem aldol-dehydration processes, this method provides mild reaction conditions to access alpha,beta-unsaturated ketones from simple, unmodified ketones. [reaction: see text]

Journal Article↗
PubMed2005

An anionic strategy for three- and four-component coupling reactions leading to ketone frameworks based on vinylogous conversion of dilithio ketone alpha,beta-dianions.

[reaction: see text] Ketone alpha,delta-dianions are generated by vinylogous extension of ketone alpha,beta-dianions with alkenes such as vinylarenes, vinylsilanes, and vinyl sulfides, which then undergo reactions at the delta and alpha positions with different electrophiles, creating ketone frameworks. This work represents a cascade-type anion method that achieved three- and four-carbon component assembly reactions leading to ketones.

Journal Article↗
PubMedDate not supplied

Neurobehavioral effects of methyl N-butyl ketone and methyl N-amyl ketone in rats and monkeys: a summary of NIOSH investigations.

The results from four NIOSH investigations concerning the neurobehavioral effects of methyl n-butyl ketone (MBK) and methyl n-amyl ketone (MAK) on experimental animals are summarized. The investigations were initiated following clinical reports of neurologic sequelae in humans exposed to these ketone solvents. In order to explore both acute and chronic effects of MBK and MAK, two general types of studies were conducted: 1) neurophysiologic evaluation of monkeys and rats following chronic inhalation, and 2) behavioral effects in rats following oral or intraperitoneal administration. Results from chronic inhalation studies after 4 months of 1000 ppm MBK exposure (all exposures: 6 hrs/day, 5 days/week) showed the following: decreased motor nerve conduction velocities (NCV) in the ulnar and sciatic-tibial nerves, reduced amplitude of evoked muscle action potentials (MAP), lengthened latency of components of the visual evoked brain potential, decreased body weight, and hindlimb drag. Decrements in sciatic-tibial NCV and MAP amplitude were found after 9 months exposure to 100 ppm MBK. In contrast, exposure to approximately 1000 ppm MAK for 9 months had no adverse affects on neurophysiologic indicators of nervous system integrity. Dose-response investigations of the effects of MBK (oral) and MAK (ip) showed for both solvents a reduction in the response rate of rats trained on a multiple schedule of reinforcement.

Action Potentials↗
PubMedDate not supplied

Pharmacodynamic and metabolic interactions between ethanol and two industrial solvents (methyl n-butyl ketone and methyl isobutyl ketone) and their principal metabolites in mice.

MnBK and MiBK prolong the duration of ketamine-, pentobarbital-, thiopental- and ethanol-induced loss of righting reflex (LRR) in mice. In equimolar doses, (5 mmol/kg i.p.), both isomers were equipotent with respect to the enhancement of ketamine-, pentobarbital-, and thiopental-induced LRR. However, MnBK was significantly more effective (twice as effective) than its isomer with respect to enhancing ethanol-induced LRR. An attempt to explain the difference in effectiveness between the two isomers was carried out. The effects of both ketones and their principal metabolites, (2-hexanol (2-HOL), 2,5-hexanedione (2,5-HD), 4-methyl-2-pentanol (4-MPOL) and 4-hydroxy 4-methyl-2-pentanone (HMP)) on ethanol-induced LRR and ethanol elimination were studied in mice. The ketones and their metabolites were dissolved in corn oil and injected intraperitoneally 30 min before 4 g/kg ethanol for LRR and 2 g/kg for ethanol elimination. Ethanol-induced LRR was significantly prolonged by the following dosages (mmol/kg), MnBK, 5; MiBK, 5; 2-HOL, 2.5; 4-MPOL, 2.5; and HMP, 2.5; 2,5-HD, 2.5, however exerted no effect. Concentrations of ethanol in blood or brain upon return of the righting reflex were similar in solvent-treated and control animals. The mean elimination rate of ethanol was slower in groups pretreated with MnBK or 2-HOL as compared to control animals. Ethanol elimination in animals pretreated with MiBK, HMP, 4-MPOL, or 2,5-HD was similar to that in control animals. These ketones are known to have some central depressant action on their own. This by itself could lead to prolongation of ethanol-induced LRR. However, MnBK, as well as one of its principal metabolites, (2-HOL), markedly reduced ethanol elimination. This could explain the observation that MnBK has a greater potentiating effect on ethanol-induced LRR that its isomer, MiBK, which does not affect ethanol elimination.

Animals↗
PubMed1987

Maximal activities of glutaminase and some enzymes of glycolysis and ketone body utilization and rates of utilization of glutamine, glucose and ketone bodies by intestinal mucosa after burn injury.

1. The effects of burn injury (33 per cent of body surface area) on the activities of key enzymes in the metabolism of glucose, glutamine and ketone bodies in the epithelial cells of the small intestine and the rates of utilization of glucose, glutamine and ketone bodies by isolated enterocytes have been investigated. 2. Burn injury decreased the maximal activities of hexokinase and 6-phosphofructokinase and increased those of glucose 6-phosphatase plus fructose bisphosphatase (in duodenum, jejunum and ileum) over the first 5 days post-injury. 3. After injury there are decreases in the rates of glucose utilization and lactate formation by incubated enterocytes. 4. The maximal activities of citrate synthase and oxoglutarate dehydrogenase were increased during the first 5 days post-injury, whereas the ketone-body-utilizing enzymes were unchanged. 5. An increase in the maximal activity of phosphate-dependent glutaminase was observed during the whole of the post-injury period studied (20 days). 6. After burn injury there is an increased rate of glutamine utilization and increased rates of formation of glutamate and alanine by incubated enterocytes.

Animals↗
PubMed1994

Metabolic fate of methyl n-butyl ketone, methyl isobutyl ketone and their metabolites in mice.

The metabolic fate of methyl n-butyl ketone (MnBK) and its isomer methyl isobutyl ketone (MiBK) was studied in mice. The concentrations of both ketones and their metabolites in blood and brain were measured at different time intervals after their administration. The principal metabolites of MnBK were 2-hexanol (2-HOL) and 2,5-hexanedione (2,5-HD), while those of MiBK were 4-methyl-2-pentanol (4-MPOL) and 4-hydroxy-4 methyl-2-pentanone (HMP). The administration of 2-hexanol by itself led to the appearance of both MnBK and 2,5-hexanedione which, when administered by itself, did not lead to the appearance of either MnBK or 2-hexanol. The administration of 4-methyl-2-pentanol resulted in the appearance of MiBK and HMP. The administration of HMP did not result in the appearance of MiBK or 4-MPOL. These results indicate that the metabolic fate of MnBK and MiBK is similar to that reported in other species.

Animals↗
PubMed2004

The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism.

The effects of ketone body metabolism suggests that mild ketosis may offer therapeutic potential in a variety of different common and rare disease states. These inferences follow directly from the metabolic effects of ketosis and the higher inherent energy present in d-beta-hydroxybutyrate relative to pyruvate, the normal mitochondrial fuel produced by glycolysis leading to an increase in the DeltaG' of ATP hydrolysis. The large categories of disease for which ketones may have therapeutic effects are:(1)diseases of substrate insufficiency or insulin resistance,(2)diseases resulting from free radical damage,(3)disease resulting from hypoxia. Current ketogenic diets are all characterized by elevations of free fatty acids, which may lead to metabolic inefficiency by activation of the PPAR system and its associated uncoupling mitochondrial uncoupling proteins. New diets comprised of ketone bodies themselves or their esters may obviate this present difficulty.

Animals↗