The potential of polycyclic aromatic hydrocarbons (PAHs) to modulate microsomal epoxide hydrolase activity, determined using benzo[a]pyrene 5-oxide as substrate, in human liver, was evaluated and compared to rat liver. Precision-cut liver slices prepared from fresh human liver were incubated with six structurally diverse PAHs, at a range of concentrations, for 24h. Of the six PAHs studied, benz...

In the context of synthetic efforts targeting the alkaloid lyconadin A, scalemic epoxide 25 was prepared by a highly stereoselective sequence involving a Myers alkylation and a Shi epoxidation. Ring-opening of this epoxide with a vinylcopper complex afforded alcohol 26 instead of the expected product 27. An unusual Lewis acid promoted Payne rearrangement of an α-trityloxy epoxide is proposed to...

The racemic mixture of 4-vinylcyclohexene (VCH) forms ovotoxic epoxides [VCH-1,2-epoxide, VCH-7,8-epoxide, and vinylcyclohexene diepoxide (VCD)] by cytochrome P450 (CYP) in B6C3F(1) female mice. These epoxides deplete primordial and primary follicles. The current studies compared in vitro epoxidation of (R)-VCH with that of (S)-VCH in hepatic microsomes prepared from adult female B6C3F(1) mice ...

Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxid...

The epoxide hydrolase activities of the 100,000 g pellet (microsomal) and 100,00 g soluble (cystosolic) fractions of mouse, rat, and guinea pig liver were measured with three closely related compounds used as substrates. Differences between the species in the distribution of the cytosolic and microsomal hydrolases and in their substrate specificities and pH optima demonstrate why epoxide hydrol...

Conversion of unsaturated fatty acids, FAMEs or triglycerides into the corresponding cyclic organic carbonates involves two reaction steps—double-bond epoxidation and CO2 insertion epoxide—that are generally conducted separately. We describe an assisted-tandem catalytic protocol able to carry out carbonation methyl oleate in one-pot without isolating epoxide intermediate. Methyl carbonate was o...

The mechanisms responsible for the gender difference in blood pressure (BP) in humans are not clear. Over the past several years we have studied the spontaneously hypertensive rat (SHR) as a model of sex differences in BP control. In the present study, we tested the hypothesis that renal vascular and microsomal epoxyeicosatrienoic acid (EET) levels are higher in females than males, and increasi...

ABSTRACT An approach to the synthesis of euonyminol, the terpenoid nucleus of the cathedulins, is described. A key step in the construction of the tricyclic core is an “epoxide cascade” which creates the tetrahydrofuran of euonyminol by a sequence of acid-catalyzed epoxide openings terminated by nucleophilic attack in the A ring. A complete regime of oxygen functionality has been installed arou...

The molecular structure and conformation of anti-3,4-dihydroxy-1,2,3,4-tetrahydronaphthalene 1,2-oxide have been determined by X-ray crystallographic techniques. This compound has been identified as a urinary metabolite of naphthalene and also mimics various metabolites of carcinogenic polyaromatic hydrocarbons. The compound crystallizes in space group Pca2(1) with cell dimensions a = 8.120(3),...