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Results for “Cyclohexanones”

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At least 343 records · Page 19Linked to original sources

PubMed2005

Antioxidant and detoxifying enzymes in the liver of rats after subchronic inhalation of the mixture of cyclic hydrocarbons.

The activity of antioxidant and detoxifying enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), the SOD isoenzyme patterns and the contents of thiobarbituric acid reactive substances (TBARS), were determined in the livers of male and female rats after subchronic inhalation of mixtures of benzene, cyclohexanone and cyclohexane. Except for decreased GSHPx (with substrate cumene hydroperoxide) and GST activities in female rats, no differences in the activities of antioxidant and detoxifying enzymes and TBARS content occurred. Between the activities of GSHPx and GST was observed an indirect relationship. The activities of GSHPx-cum and GST were influenced by sex.

Animals↗

PubMed1975

Gas chromatographic-mass spectrometric study of volatile organic metabolites in urines of patients with diabetes mellitus.

Abnormally increased concentrations of the aliphatic alcohols ethanol, n-propanol, isobutanol, n-butanol and isopentanol and the ketones 4-heptanone and cyclohexanone in human urine reflect metabolic disorders related to diabetes mellitus. For the determination of these low-molecular-weight metabolites, the components are trapped on an absorbent, separated by gas chromatography and identified by mass spectrometry. After standardization of the adsorption and desorption techniques, the procedure is applicable for comparative studies and for screening.

1-Propanol↗

PubMed2002

In vitro co-metabolism of ethanol and cyclic ketones.

The paper presents the results of studies concerning the effects of four cyclic ketones, i.e. cyclopentanone (Pen), cyclohexanone (Hex), cycloheptanone (Hep) and cyclooctanone (Oct) on metabolism of ethanol (EtOH) in vitro. The fraction S9 (supernatant with the removed mitochondria) was used obtained from homogenized rat livers. An increase in reduced nicotinamide adenine dinucleotide (NADH) was examined spectrophotometrically (at 340 nm) while the substrate disappearance and metabolite increase were determined using head-space gas chromatography. The addition of cyclic ketones statistically significantly affected a decrease in the A(340) level, particularly during co-metabolism of EtOH and Hex. The EtOH loss was significantly higher (than the loss observed during metabolism of EtOH alone) only in EtOH-Hex and EtOH-Hep systems, which may be explained by the fact that reoxidation of NADH to NAD+ is quicker in these systems than dissociation of the alcohol dehydrogenase (ADH)-NADH complex.

Alcohol Dehydrogenase↗

PubMed1981

Mechanistic deductions from isotope effects in multireactant enzyme mechanisms.

In the enzymatic mechanism with two or more substrates, comparison of the isotope effects on the maximum velocity and on the apparent V/K values when each substrate concentration is varied allows one to deduce the kinetic mechanism and obtain quantitative information on the relative rates at which substrates dissociate from the enzyme, as opposed to undergoing reaction to give products. Theory is also presented for using the effects of other reactants on the apparent isotope effects determined by the equilibrium perturbation method to determine the same information. With liver alochol dehydrogenase, DPN is not released at an appreciable rate from the E-DPN-cyclohexanol complex, while cyclohexanol is released much more rapidly than it reacts to give products, so that the mechanism appears ordered. With DPNH and cyclohexanone, however, the reaction is random since DPNH can be released from the ternary complex at a finite rate. With yeast alcohol dehydrogenase, acetone, when present, prevents DPNH release from the enzyme so that the mechanism at equal rates from E-DPN-2-propanol so tht the reaction is random in this direction.

Alcohol Oxidoreductases↗

PubMed2002

Identification of a new class of inhibitors of the voltage-gated potassium channel, Kv1.3, with immunosuppressant properties.

The voltage-gated potassium channel, K(v)1.3, is a novel target for development of immunosuppressants. Using a functional (86)Rb(+) efflux assay, a new class of high-affinity K(v)1.3 inhibitors has been identified. The initial active in this series, 4-phenyl-4-[3-(2-methoxyphenyl)-3-oxo-2-azaprop-1-yl]cyclohexanone (PAC), which is representative of a disubstituted cyclohexyl (DSC) template, displays a K(i) of ca. 300 nM and a Hill coefficient near 2 in the flux assay and in voltage clamp recordings of K(v)1.3 channels in human T-lymphocytes. PAC displays excellent specificity as it only blocks members of the K(v)1 family of potassium channels but does not affect many other types of ion channels, receptors, or enzyme systems. Block of K(v)1.3 by DSC analogues occurs with a well-defined structure-activity relationship. Substitution at the C-1 ketone of PAC generates trans (down) and cis (up) isomer pairs. Whereas many DSC derivatives do not display selectivity in their interaction with different K(v)1.x channels, trans DSC derivatives distinguish between K(v)1.x channels based on their rates of C-type inactivation. DSC analogues reversibly inhibit the Ca(2+)-dependent pathway of T cell activation in in vitro assays. Together, these data suggest that DSC derivatives represent a new class of immunosuppressant agents and that specific interactions of trans DSC analogues with channel conformations related to C-type inactivation may permit development of selective K(v)1.3 channel inhibitors useful for the safe treatment of autoimmune diseases.

Alanine↗

PubMed2003

Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolecular aldol reactions.

Quantum mechanical calculations were employed to predict the ratio of four stereoisomeric products expected from two complex reactions involving the aldol reactions of cyclohexanone with benzaldehyde or with isobutyraldehyde catalyzed by (S)-proline. Experimental tests of these predictions provide an assessment of the state-of-the-art in quantum mechanical prediction of products of complex organic reactions in solution.

Alcohols↗

PubMed2003

Lithium diisopropylamide-mediated lithiations of imines: insights into highly structure-dependent rates and selectivities.

Lithium diisopropylamide-mediated lithiations of N-alkyl ketimines derived from cyclohexanones reveal that simple substitutions on the N-alkyl side chain and the 2-position of the cyclohexyl moiety afford a 60,000-fold range of rates. Detailed rate studies implicate monosolvated monomers at the rate-limiting transition structures in all instances. Comparisons of experimentally derived regioselectivities and rates, taken in conjunction with density functional theory computational studies, reveal a number of factors that influence reactivities including: (a) axial versus equatorial disposition of the proton on the cyclohexane ring, (b) syn versus anti orientation of the lithiation relative to the N-alkyl group, (c) the presence or absence of a potentially chelating methoxy moiety on the N-alkyl group, (d) the presence of a 2-methyl substituent at the geminal or distal alpha-carbon, and (e) branching in the N-alkyl group. The isolated contributions are not large, yet they display a strong and predictable additivity leading to a kinetic resolution of imines derived from racemic 2-methylcyclohexanone.

Cyclohexanones↗

PubMed2003

Asymmetric Schmidt reaction of hydroxyalkyl azides with ketones.

An asymmetric equivalent of the Schmidt reaction permits stereocontrol in ring expansions of symmetrical cyclohexanones. The procedure involves the reaction of chiral 1,2- and 1,3-hydroxyalkyl azides with ketones under acid catalysis; the initial reaction affords an iminium ether that can be subsequently opened with base. A systematic study of this reaction is reported, in which ketone substrates, chiral hydroxyalkyl azides, and reaction conditions are varied. Selectivities as high as ca. 98:2 are possible for the synthesis of substituted caprolactams, with up to 1,7-stereoselection involved in the overall process. The fact that either possible migrating carbon is electronically identical provides an unusual opportunity to study a ring-expansion reaction controlled entirely by stereoelectronic factors. The mechanism of the reaction and the source of its stereoselectivity are also discussed.

Azides↗

PubMed2003

Unusual tethering effects in the Schmidt reaction of hydroxyalkyl azides with ketones: cation-pi and steric stabilization of a pseudoaxial phenyl group.

The Lewis acid-promoted reactions of chiral 2-aryl-3-azido-1-propanols with 4-substituted cyclohexanones lead to iminium ethers and ultimately caprolactams (following a hydrolysis step). In this study, it is shown that these reactions afford variable ratios of products, depending on the electronic nature of the phenyl group. These results are interpreted in the context of a cation-pi stabilizing effect in the product-determining reaction intermediate. Remarkably, the best selectivity was obtained when an azidopropanol reagent containing a quaternary center was used; a control experiment showed that the high selectivity observed in this result depended upon the free rotation of the pseudoaxial aromatic group in the intermediate that affords the major product.

Azides↗

PubMed2005

Selective inhibitors of the serine protease plasmin: probing the S3 and S3' subsites using a combinatorial library.

A combinatorial library of 400 serine protease inhibitors with the general structure Cbz-X(aa)-Trp-cyclohexanone-Trp-Y(aa)-OH has been constructed. The library was synthesized on the solid phase using mix-and-split synthesis, where 20 different amino acids were incorporated at both the X(aa) and Y(aa) positions. These two positions correspond to the S3 and S3' subsites of the active site. Iterative deconvolution was used to identify hits from the library. The library was screened against four serine proteases: plasmin, kallikrein, thrombin, and trypsin. Seven inhibitors from the library that showed promising activities were resynthesized using solution-phase methods. Four of these compounds were good inhibitors of plasmin with IC(50) values in the range of 2.7-3.6 microM. The most potent of these inhibitors showed >150-fold selectivity for plasmin when compared to the other three serine proteases.

Combinatorial Chemistry Techniques↗

PubMed2002

Inhibitors of plasmin that extend into both the S and S' binding sites: cooperative interactions between S1 and S2.

A new procedure for the synthesis of cyclohexanone-based inhibitors of serine proteases is reported. In this procedure the reactive ketone functionality is carried through the synthesis in masked form as a TBDMS-protected alcohol. Deprotection followed by oxidation of the alcohol generates the final form of the inhibitor. Two new inhibitors, which interact with the S1-S3 and S2' subsites of plasmin, are synthesized using this procedure. Inhibitors 1 and 2 have IC50 values against plasmin of 20 and 24 microM, respectively. The inhibition studies show that cooperative binding of inhibitors in the S1 and S2 subsites of plasmin is important for determining inhibitor selectivity.

Binding Sites↗

PubMed2005

Enantioselective approaches to potential MetAP-2 reversible inhibitors.

[reaction: see text] Enantioselective deprotonation of 4-substituted cyclohexanones and highly stereoselective conjugate addition of higher order mixed cuprates were the key steps in a concise synthesis of fumagalone-related molecules. The origin of the (low) biological activity of the new compounds as compared to fumagalone is briefly discussed.

Aminopeptidases↗

PubMed2005

Ammonia-promoted fragmentation of 2-alkyl- and 2,4-dialkyl-3-iodo-1- oxocyclohexan-2,4-carbolactones.

2-Alkyl- and 2,4-dialkyl-3-iodo-1-oxocyclohexan-2,4-carbolactones undergo ammonia-promoted fragmentation reactions to provide butenolides, gamma-butyrolactone, and/or beta,gamma-epoxycyclohexanones. Product distribution is governed by the relative size of the substituents at C-2 and C-4 of the cyclohexanones. Butenolide amide, the major product from the fragmentation, is further converted into their respective piperidinone and pyrrolidine derivatives.

Ammonia↗

PubMed2005

Tandem Sakurai-aldol addition reactions as a route to structurally complex carbocycles.

Tandem intramolecular Sakurai-aldol reactions provide a concise and highly diastereoselective route to substituted cyclohexenone derivatives. The cyclization substrates are readily obtained using olefin isomerization-Claisen rearrangement (ICR) reactions to prepare the key chiral allyl silane precursors. The Claisen reaction products are elaborated to the chiral Sakurai-aldol substrates by an efficient two-step sequence involving vinyl organometallic-aldehyde addition and oxidation of the resulting alcohol. The reaction of the resulting enones with TiCl(4) elicits a highly stereoselective allyl silane conjugate addition to produce a trichlorotitanium enolate as the reaction intermediate; intermolecular trapping of the enolate with an aldehyde provides pentasubstituted cyclohexanone derivatives in which the annulation reaction establishes four stereocenters and two new C-C bonds. A fully intramolecular variant of the Sakurai-aldol reaction that creates four stereocenters, two new C-C bonds, and establishes two new carbocyclic rings is also described.

Alkenes↗

PubMed2006

Designing new Baeyer-Villiger monooxygenases using restricted CASTing.

This paper outlines the design and execution of the first mini-evolution of cyclopentanone monooxygenase (CPMO). The methodology described is a relatively inexpensive and rapid way to obtain mutant enzymes with the desired characteristics. Several successful mutants with enhanced enantioselectivities were identified. For example, mutant-catalyzed oxidation of 4-methoxycyclohexanone gave the corresponding lactone with 92% entantiometric excess (ee) compared to the 46% ee achieved with wild-type cyclohexanone monoxygenase (WT-CHMO). The original design of the mini-evolution and the following evaluation of mutants can provide valuable insights into the active site's construction and dynamics and can suggest other catalytically profitable mutations within the putative active site.

Amino Acid Sequence↗

PubMed2000

A cyclohexanonyl bromophenol from the red alga Symphyocladia latiuscula.

From an extract of the red alga Symphyocladia latiuscula, a bromophenol (1) was isolated and characterized as (2R)-2-(2,3, 6-tribromo-4,5-dihydroxybenzyl)-cyclohexanone based on the spectroscopic evidence. The bromophenol was found to be a scavenger of 1,1-diphenyl-2-picrylhydrazyl radical.

Bromine↗

PubMed2005

Asymmetric synthesis of 5-arylcyclohexenones by rhodium(I)-catalyzed conjugate arylation of racemic 5-(trimethylsilyl)cyclohexenone with arylboronic acids.

[reaction: see text] A catalytic asymmetric conjugate arylation of racemic 5-(trimethylsilyl)cyclohex-2-enone with arylboronic acids was catalyzed by 3 mol % chiral amidophosphane- or BINAP-Rh(I) in dioxane-water (10:1) to afford trans- and cis-3-aryl-5-(trimethylsilyl)cyclohexanones in high enantioselectivity. Dehydrosilylation of the product mixture with cupric chloride in DMF gave 5-arylcyclohex-2-enones with up to 93% ee in good yield. Enantiofacial selectivity with chiral phosphane-Rh(I) exceeds the trans-diastereoselectivity that is maintained in the achiral or racemic phosphane-Rh(I)-catalyzed conjugate arylation of 5-(trimethylsilyl)cyclohexenone.

Boronic Acids↗

PubMed2005

Readily tunable and bifunctional L-prolinamide derivatives: design and application in the direct enantioselective Aldol reactions.

[reaction: see text] Readily tunable and bifunctional L-prolinamides as novel organocatalysts have been developed, and their catalytic activities were evaluated in the direct asymmetric Aldol reactions of various aromatic aldehydes and cyclohexanone. High isolated yields (up to 94%), enantioselectivities (up to 99% ee), and anti-diastereoselectivities (up to 99:1) were obtained under the optimal conditions.

Aldehydes↗