Diol metabolites

Allen CCR, DR Boyd, H Dalton, ND Sharma, I Brannigan, NA Kerley, GN Sheldrake, SC Taylor (1995) Enantioselective bacterial biotransformation routes to cw-diol metabolites of monosubstituted benzenes, naphthalene and benzocycloalkenes of either absolute configuration. J Chem Soc Chem Commun 117-118. 

BaP 7.8.9.10-tetrahydro-trans-9.10-diol (1.0 A2A /ml, derived from BaP trans-9.10-dihvdrodiol metabolite), and BaP trans-4.5-dihvdro-diol metabolite (1.0 A270 m CD spectra are expressed by ellipti-city at the indicated concentration as described (9.50). Ar = p-N,N-dimethylaminobenzoyl. 

Fig. 10.17. The epoxide-diol pathway in 5-vinylbarbitu.rates such as vinylbital (10.65, R = 1-methylbutyl). The difference with 5-allylbarbiturates is that the diol metabolite of 5-vinylbar-biturates cannot be isolated due to its immediate decomposition via a retro-aldol-type reaction...

The absorption and elimination of epichlorohydrin in mice are rapid after oral administration. The diol metabolite, 3-chloro-l,2-propanediol, was detected in plasma (Rossi et al., 1983a). 

To date, the only natural product containing a benzene dioxide moiety is the antibiotic 149. In addition to this cis dioxide, there is evidence that trans naphthalene dioxide 152 may be an intermediate in the hepatic metabolism of naphthalene. The reactivity of the cis (153) and trans (152) naphthalene dioxides with nucleophiles and the relative stereochemistry of the adducts has been determined. The possibility that arene dioxide intermediates form during metabolism of PAHs has been discussed frequently. Indeed, the detection of a rrans-diol epoxide such as that derived from arene oxide 25, or the isolation of a rra s-diol oxepin (e.g., 165) is mechanistically consistent with the formation of two epoxides on either the same or different rings. However, presently available evidence would suggest that it is most unlikely that either diol metabolite was derived from an arene dioxide intermediate. Involvement of dioxide intermediates in the metabolism of PAHs will require further experimental verification. 

Rambeck, B., May, T, Juergens, U. Serum concentrations of car-bamazepine and its epoxide and diol metabolites in epileptic patients the influence of dose and comedication. Ther. Drug Monit. 1987, 9, 298-303. 

Dinitrobenzoyl chloride Benzoyl chloride, 3,5-dinitro- (99-33-2), 76, 277 2,4-Dinitrofluorobenzene, 76, 52 Diol metabolites, 76, 82 Dioxaborolane ligand, 76, 89... 

M Asami, M Yamamura, W Takasaki, Y Tanaka. Quantitative determination of diol metabolites of CS-670, a new antiinflammatory agent, by capillary column gas chromatography-mass spectrometry. J Chromatogr B 665 107, 1995. 

EPHXs are important multifunctional enzymes from both the deactivation and activation of reactive species. Furthermore, they convert any potentially reactive epoxide formed by the P450s system into a diol metabolite, which is usually less reactive, more water soluble, and more easily cleared by GSTs. There are two major types of EPHX enzymes the microsomal (mEPHX), which uses epoxides of polycyclic aromatics or drugs as substrates (type 1) and which controls hepatic uptake of bile acids (type 2) [67], and the soluble EPHX (sEPHX), which forms diols from many endogenous and exogenous epoxides, including fatty acids and leukotrienes [68],... 

Over 300 diol metabolites are known.8 Several diols and some secondary synthons derived from them have recently become commercially available Eastman Fine Chemicals, Genencor (1 S-cis)-3-Chloro-3,5-cyclohexadiene-1,2-diol, (1 S-cis)-3-bromo-3,5-cyclohexadiene-1,2-diol, (1 S-cis)-3-iodo-3,5-cyclohexadiene-1,2-diol, (5S-cis)-5,6-dihydroxy-1,3-cyclohexadiene-1 -carbonitrile, cis-2R,3S-2,3-dihydroxy-2,3-dihydrobenzonitrile acetonide, (1R-cis)-1,2-dihydro-1,2-naphthalenediol, (1R-cis)-1,2,3,4-tetrahydro-1,2-naphthalenediol, (4S-trans)-4,5-dihydroxy-3-oxo-1 -cyclo-hexene-1-carboxylic acid, furo[3,4-d]-1,3-dioxol-4(3aH)-1 -dihydro-6-hydroxy-2,2-dimethyl-[3aR-(3aa,6aa)]. 

Over 300 diol metabolites are known. Several diols and some secondary synthons derived from them have recently become commercially available Eastman Fine Chemicals, Genencor (1 S-cis)-3-Chloro-3,5-cyclohexadiene-1,2-diol, (1S-cis)-... 

It has also been suggested that valproate is not a selective inhibitor of epoxide hydrolase but that it inhibits all the steps of the epoxide-diol pathway. The trans-diol metabolite is then further converted by glueuronida-tion, and it seems that this step is also inhibited. ... 

Sunaoshi W, Miura H, Takanashi S, Shira H, HosodaN. Influence of concurrent administta-tion of sodium valproate on the plasma concentrations of carbamazepine and its epoxide and diol metabolites. JpnJPsychiatry Neurol (1991) 45, 474-7. 

Epoxidation by the introduction of an oxygen atom into flunarizine produced l-[bis(4-fluoro-phenyl)methyl] - 4 - [(3-phenyloxiran - 2 - yl)methyl] piperazine (metabolite 2) and epoxide hydration to a diol, 3-[4-[bis(4-fluorophenyl)methyl]-l-piper-azinyl]-l-phenyl-l,2-propanediol (metabolite 10). Lavrijsen et al. (1992) found metabolites formed by epoxidation at the double bond (metabolite 2) and epoxide hydration (metabolite 10) in incubates with subcellular hepatocyte fractions of male and female rats. Metabolites formed by epoxidation and epoxide hydration were not detected in vivo (Meuldermans et al. 1983), probably because the resulting metabolites were metabolised in vivo, much more quickly than in vitro, into secondary metabolites. A diol metabolite, however, was described for the metabolism of l-butyl-4-dimamyl-piperazine in guinea pigs (Morishita et al. 1978). With supernatant fractions a rapid disappearance of the epoxide intermediate from incubate was observed. This seems to indicate that, for the epoxide hydrolysis, besides microsomal epoxide hydrolase, cytosolic epoxide hydrolase might also be involved. 

TABLE 1. Incubation of the drugs, under various experimental conditions with rat liver microsomes, showing the enzymatic formation of epoxide and diol metabolites,... 

Boronate derivatives, diol metabolites of tricyclic drugs, 255 - 3-methoxy-4-hydroxy-phenylethyleneglycol, 216-218... 

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