Cecilia Cortez

Syntheses of 2-Bromopyrene and 2-Hydroxypyrene

Abstract Regiospecific monobromination of 4,5,9,10-tetrahydropyrene in the 2-posiuon is accomplished in aqueous dimethylformamide. Conversion of the previously unknown 2-bromo-4,5,9,10-tetrahydropyrene to the title compounds is described.

Fluorine-substituted derivatives of the carcinogenic dihydrodiol and diol epoxide metabolites of 7-methyl-, 12-methyl- and 7,12-dimethylbenz[a]anthracene

Abstract Stereospecific syntheses of the trans-3,4-dihydrodiol metabolites of 9- and 10-fluoro-7,12-dimethylbenz[a]anthracene, -7-methylbenz[a]anthracene, and -12-methylbenz[a]anthracene are described. These dihydrodiols are putative proximate carcinogenic metabolites that undergo activation by the P-450 microsomal enzymes to ultimate carcinogenic anti- and syn-diol epoxide metabolites that bind to nucleic acids in vivo. Syntheses of several of the anti- diol epoxide metabolites are also described.

Syntheses of “unstable” diol epoxide metabolites of the potent carcinogens 7- and 12-methylbenz[a]anthracene

Abstract Stereospecific syntheses of the anti- and syn-diol epoxides of 7- and 12-methylbenz[a]anthracene, suspected as active metabolites of the parent PAHs but previously thought to be too chemically reactive and unstable to isolate, are described and the pure compounds are shown to be moderately stable.

A new coumarin synthesis based on the aromatic metalation reaction

Abstract A convenient synthetic approach to coumarins and polycyclic coumarins based on the aromatic metalation reaction is described. Several polycyclic coumarins exhibit strong anticarcinogenic activity.

DNA Adducts from syn 7-Methylbenz[A]anthracene 3,4-Dihydrodiol 1,2-Epoxide

Abstract DNA adducts derived from reaction of the racemic bay region syn 7-methylbenz[a]anthracene 3,4-dihydrodiol 1,2-epoxide with calf thymus DNA in vitro were tentatively identified. Eight markers (four deoxyguanosine and four deoxyadenosine adducts) were obtained from separate reactions of the racemic syn dihydrodiol epoxide with deoxyguanylic and deoxyadenylic acids. The nucleoside of origin of individual DNA products was established by comparing HPLC retention times and UV spectra of DNA adducts with those of the adduct markers. All DNA adducts eluted with retention times and had UV spectra that corresponded to the purine nucleoside adducts. Circular dichroism spectra of the marker adducts allowed assignment of S and R configuration at C1, the site of attachment of the hydrocarbon residue to the nucleoside. The CD spectra were comprised of four pairs of spectra that were mirror images of one another. Each pair consisted of the two cis or two trans products resulting from epoxide ring opening of each...

Utilization of the deuterium isotope effect to suppress enolization during alkylation of ketones

A substantial enhancement in yield is observed in the reaction of enolizable ketones with the lithium salt of N,N-diethylbenzamide and N,N-diethyl-1-naphthamide when the hydrogen atoms α to the carbonyl group are replaced with deuterium.

Synthesis of biologically active dihydrodiol metabolites of 16,17-dihydro-15H-cyclopenta[a]phenanthrene and its carcinogenic 11-methyl and 17-keto derivatives

Abstract Syntheses are described of the trans-3,4-dihydrodiol metabolites of the title compounds implicated by biological studies as proximate carcinogenic forms that give rise to the corresponding diol epoxide metabolites that bind covalently to DNA in vivo.