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...

Distribution of epoxide hydrolase activity in subcellular fractions of livers from male Swiss-Webster mice and Sprague-Dawley rats was monitored with trans-B-ethylstyrene oxide, mznsstilbene oxide and benzo[a]pyrene 4,5-oxide following differential centrifugation. With the former two substrates the highest activity was encountered in the cytosolic fraction; however, significant activity was fou...

Sodium selenite inhibits the binding of 7,12-dimethylbenz(a)anthracene (DMBA) to DNA in tertiary cultures of fetal mouse cells in a rather selective fashion. Inhibition can be demonstrated at 6 but not at 3 h after DMBA addition to the cells. Inhibition is seen after treatment of the cells with DMBA concentrations of 0.05 or 0.1 micrograms/ml but not after treatment at 0.01 micrograms/ml. Furth...

Membrane-bound and soluble epoxide hydrolase activities in the mononuclear cell fraction from human blood have been characterized using cis- and trans-stilbene oxides as substrates, respectively. Because of the low activities in these cells, it was necessary to modify assay procedures developed for rat and mouse liver in the following ways: (a) the substrates were relatively highly labeled (2 C...

Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (+/-)-7beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. The mutagenicity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 in strain TA10...

A clofibrate-induced mouse liver cDNA library was prepared and used to isolate the coding sequence for soluble epoxide hydrolase. A 1668-base pair (bp) clone was isolated and found to contain a 1269-bp open reading frame coding for 423 amino acids. Subsequent RNA polymerase chain reaction resulted in the isolation of 396 bp of additional 5'-sequence. Translation of the resulting 1659-bp open re...