Search results for "epoxide"

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-?-rotunol and All Diastereomers of 6,11-Spirovetivadiene.

2005

The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has been achieved starting from santonin. The key step is the silicon-guided acid-promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from santonin in several steps involving lactone reductive opening, conjugate addition of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after elimination of the primary hydroxyl group in the side chain, followed…

The enzymatic mechanism of epoxide hydrolysis

1995

Methacrylate monolithic columns functionalized with epinephrine for capillary electrochromatography applications.

2013

Epinephrine-bonded polymeric monoliths for capillary electrochromatography (CEC) were developed by nucleophilic substitution reaction of epoxide groups of poly(glycidyl-methacrylate-co-ethylenedimethacrylate) (poly(GMA-co-EDMA)) monoliths using epinephrine as nucleophilic reagent. The ring opening reaction under dynamic conditions was optimized. Successful chemical modification of the monolith surface was ascertained by in situ Raman spectroscopy characterization. In addition, the amount of epinephrine groups that was bound to the monolith surface was evaluated by oxidation of the catechol groups with Ce(IV), followed by spectrophotometric measurement of unreacted Ce(IV). About 9% of all th…

Peroxisomes and Hepatotoxicity

1995

Peroxisomes are ubiquitous organelles of eukaryotic cells and are present in significant amounts in hepatic liver cells. Peroxisomal enzymes contribute to several metabolic pathways including fatty acid, purine and amino acid catabolism or bile acid synthesis. The peroxisomal oxidative reactions produce hydrogen peroxide, mostly degraded by catalase which prevents oxidative stress. Moreover, peroxisomes are involved in arylderivative drug detoxification through its epoxide hydrolase activity.

Epoxide Hydrolases: Structure, Function, Mechanism, and Assay

2005

Epoxide hydrolases are a class of enzymes important in the detoxification of genotoxic compounds, as well as in the control of physiological signaling molecules. This chapter gives an overview on the function, structure, and enzymatic mechanism of structurally characterized epoxide hydrolases and describes selected assays for the quantification of epoxide hydrolase activity.

Importance of Individual Enzymes in the Control of Ultimate Carcinogens

1995

The metabolic activation of most chemical mutagens and carcinogens is a prerequisite for their mutagenic and carcinogenic activity. Reactive metabolites are under the control of activating, inactivating and precursor sequestering enzymes. These enzymes are under the long-term control of induction and repression and under the short-term control of posttranslational modification. As far as carcinogen-metabolizing enzymes are concerned, posttranslational modification has received little attention. This short-term regulation may be especially important since it works fast and may affect the enzymatic activity as well as the degradation of the enzyme. The enzymatic activity is modified by activa…

Detoxication Strategy of Epoxide Hydrolase—The Basis for a Novel Threshold for Definable Genotoxic Carcinogens

2004

From our recent work on the three-dimensional structure of epoxide hydrolases we theoretically deduced the likelihood of a two-step catalytic mechanism that we and others have subsequently experimentally confirmed. Analysis of the rate of the two steps by us and by others show that the first step—responsible for removal of the reactive epoxide from the system—works extraordinarily fast (typically three orders of magnitude faster than the second step), sucking up the epoxide like a sponge. Regeneration of the free enzyme (the second step of the catalytic mechanism) is slow. This becomes a toxicological problem only at doses of the epoxide that titrate the enzyme out. Our genotoxicity work s…

Significance of various enzymes in the control of reactive metabolites

1987

Most chemical carcinogens are relatively inert and need metabolic activation to the ultimately carcinogenic species. The concentration of such species is controlled by several different enzymes. Especially well studied is the important group of enzymes responsible for the control of reactive epoxides. Many natural, as well as man-made foreign compounds, including pharmaceuticals, possess olefinic or aromatic double bonds. Such compounds can be transformed to epoxides by microsomal monooxygenases present in many mammalian organs. By virtue of their electrophilic reactivity, such epoxides may spontaneously react with nucleophilic centres in the cell and thus covalently bind to DNA, RNA and pr…

Can Experimental Electron-Density Studies be Used as a Tool to Predict Biologically Relevant Properties of Low-Molecular Weight Enzyme Ligands?

2013

The case of protease inhibitor model compounds incorporating an aziridine or epoxide ring is used to exemplify how application of experimental electron-density techniques can be used to explain the biological properties of low-molecular weight enzyme ligands. This is furthermore seen in the light of a comparison of crystal and enzyme environments employing QM/MM computations to elucidate to which extent the properties in the crystal can be used to predict behavior in the biological surrounding.

Purification of rat liver epoxide hydratase to apparent homogeneity.

1975

Epoxide hydratase (EC 4.2.1.63) is a microsomal enzyme which catalyses the conversion of epoxides to trans-dihydrodiols. Epoxides, produced by the action of microsomal monooxygenases (EC 1.14.1.1) from aromatic and olefinic compounds, are thought to be responsible for many of the harinful effects of polycyclic hydrocarbons and related compounds. Thus epoxide hydratase, together with glutathione 9transferases, (EC 2.5.1.18) may play an important role in the removal of carcinogenic and cytotoxic metabolites (for reviews see [l-3]). It has been reported [4,5] that dihydrodiols formed from some polycyclic hydrocarbons (benz(a)anthracene and benzo(a)pyrene) are reactivated by the microsomal mono…