Diol epoxides relationship

These results can now be used to consider what happens when a diol epoxide attacks DNA. The epoxide group will open and trans addition will occur. The product (XXVI) will have the DNA substituted adjacent to the bay region (particularly if it is hindered so that the epoxide group is made more reactive) and will lie axial to the PAH ring system. This means that the plane of the PAH and the alkylated base of DNA must have a perpendicular relationship to each other as indicated in Figure 19. In this Figure those sites in... 

Model computational studies aimed at understanding structure-reactivity relationships and substituent effects on carbocation stability for aza-PAHs derivatives were performed by density functional theory (DFT). Comparisons were made with the biological activity data when available. Protonation of the epoxides and diol epoxides, and subsequent epoxide ring opening reactions were analyzed for several families of compounds. Bay-region carbocations were formed via the O-protonated epoxides in barrierless processes. Relative carbocation stabilities were determined in the gas phase and in water as solvent (by the PCM method). 

Phillips DH, Hewer A, Seidel A, et al. 1991. Relationship between mutagenicity and DNA adduct formation in mammalian cells for fjord- and bay-region diol-epoxides of polycyclic aromatic hydrocarbons. Chem Biol Interact 1991 80(2) 177-186. 

The diol epoxide pathway does, however, account for the structure-activity relationships in the bay region, methylated bay region, and fjord region PAH, since diol epoxides would not form without this structural feature. 

Abbreviations PAH, polycyclic aromatic hydrocarbon DE, diol epoxide PAHDE, polycyclic aromatic hydrocarbon diol epoxide PAHTC, polycyclic aromatic hydrocarbon triol carbocation TC, triol carbocation BaP, benzo[a]pyrene BeP, benzo[e]pyrene BA, benz[a]anthracene DBA, dibenz[a,h]anthracene BcPh, benzo[c)phenanthrene Ch, chrysene MCh, methylchrysene MBA, 7-methyl benz[a]anthracene DMBA, 7,12-dimethyl benz[a]anthracene EBA, 7-ethyl benz[a]anthracene DB(a,l)P, dibenzo[a,l]pyrene MSCR, mechanism-based structure-carcinogenicity relationship PMO, Perturbational molecular orbital method dA, deoxyadenosine dC, deoxycytosine dG, deoxyguanosine MOS, monoxygenase enzyme system EH, epoxide hydrolase enzyme system N2(G), exocyclic nitrogen of guanine C, electrophilic centre of PAHTC K, intercalation constant CD, circular dichroism LD, linear dichroism. 

The proposed dinuclear transition-state model (1) has been supported by the observation of nonlinear relationship between enantiomeric excess (ee) of the epoxide and ee of DAT.33 The use of simple diol instead of tartrate vitiates stereoselectivity of the reaction.34,35 The ester group of DAT is indispensable for the construction of the desired catalyst. It is noteworthy that 1,2-di(o-methoxy-phenyl)ethylenediol is an efficient chiral auxiliary for titanium-mediated epoxidation, while 1,2-diphenylethylenediol is a poor one.36... 

D. A. Svinarov, C. E. Pippenger, Relationships between Carbamazepine-Diol, Carba-mazepine-Epoxide, and Carbamazepine Total and Free Steady-State Concentrations in Epileptic Patients The Influence of Age, Sex, and Comedication , Ther. Drug Monit. 1996,18, 660 - 665. 

This mechanistically fascinating product can be explained by the initial formation of a cyclic chromate ester, facilitated by the formation of a five-membered ling and the (cis) relationship in the 1,2-diol. Interestingly, this stable chromate does not evolve resulting in the oxidation of the secondary alcohol, but it suffers elimination producing a very electron-rich benzyloxy alkene that is easily epoxidized intramolecularly by chromium. Observe that the epoxide oxygen enters from the same face than the secondary alcohol. 

Since the hydroxyl groups in the diol product have a trans relationship, the product can only be formed by epoxide hydrolysis. (Treatment of the alkene with OsC>4 yields a product in which the two -OH groups have a cis relationship.)... 

Strategy Notice the relationship of the hydroxyl groups in the two diols. In diol (a), the two hydroxyls are cis, and in (b) they are trans. Since ring-opening of epoxides forms trans -1,2-diols, only diol (b) can be formed by this route. The cw-I,2-diol in (a), results from treatment of 1-methylcyclohexene with OsO The enantiomers of the diols are also formed. 

In their first and racemic synthesis of methyl nonactate 75 (Scheme 8), Bartlett and Jernstedt (18) introduced the 1,3-relationship between C-6 and C-8 in a diastereoselective manner from the diene 68, which gave the analogous cyclic phosphate. Upon treatment with sodium methoxide, the phosphate gave the epoxide 69, which was converted into the syn-1,3-diol 70. Acetylation of the diol followed by ozonolysis gave the aldehyde 71. Aldol condensation of the aldehyde with the silyl... 

Many nucleophiles react with epoxides. The reaction of an epoxide and NaOH will lead to a diol, and the reaction with sodium cyanide will give a product containing an OH unit and a CN unit (a cyanohydrin). When 133 reacts with NaOH, for example, the product after hydrolysis is cyclohexanediol (134). Note the irons relationship of the two hydroxyl units, which result from backside attack of hydroxide at the epoxide. When 2(S)-2-ethyloxirane (135) reacts with NaCN in DMF (the solvent), the resultant alkoxide (136) shows retention of the stereogenic center at C2 because attack occurs at the less substituted Cl atom. An aqueous acid workup gives the cyanohydrin product, 137. 

Epoxides. Vicinal diols, capable of attaining an antiperipla-nar relationship, can be converted to epoxides (eq 2). The reaction requires 1-2 equiv of (1) in chloroform, ether, or carbon tetrachloride and takes place at rt. The reaction is postulated to take place via ligand exchange with the sulfone followed by decomposition to the epoxide, diphenyl sulfoxide, and 1,1,1,3,3,3-hexafluoro-2-phenylisopropanol. 

RELATIONSHIP BETWEEN STRUCTURE AND METABOLISM OF TRICYCLIC DRUGS STABLE EPOXIDE-DIOL PATHWAY... 

The precursor relationships of hydrocarbons XLVI and LXIX were next examined with respect to the other metabohtes with which they occur, epoxide, diol and chlorhydrin. When XLVI, marked in the end methylene group was fed to Centaurea ruthenica Lam., the chlorhydrin XLIX and its acetate were radioactive and it was found on degradation that the end (oxygen bearing) carbon accounted for essentially the total activity of the molecule (Bohlmann and Hinz, 1964). In another experiment (Bohlmann, Hinz, Seyberlich and Repplinger, 1964), in which the tetra5mediene (LXXI) was used as precursor, an analogous result was obtained. The chlorhydrin (LXXII) and its acetate (LXXIII), which occur naturally in the plant, were radioactively marked, exclusively in the end carbon. 

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