Stereochemistry of the major rodent liver microsomal metabolites of the carcinogen dibenz(a,j)acridine

Journal Article · · Chemical Research in Toxicology; (USA)

DOI:https://doi.org/10.1021/tx00005a007· OSTI ID:5182425

Duke, C C; Holder, G M; Rosario, C A; Ryan, A J ^[1]

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1. Univ. of Sydney (Australia)

The major metabolites of the carcinogen dibenz(a,j)acridine formed in rodent liver microsomal preparations were trans-3,4-dihydroxy-3,4-dihydrodibenz(a,j)acridine (DBAJAC-3,4-DHD) and dibenz(a,j)acridine 5,6-oxide (DBAJAC 5,6-oxide). The enantiomers of DBAJAC-3,4-DHD were prepared from the separable diastereoisomeric esters with (+)-endo-1,4,5,6,7,7-hexachlorobicyclo(2.2.1)hept-5-ene-2-carboxylic acid (HCA). The absolute configuration of trans-3(R),4(R)-dihydroxy-1,2,3,4-tetrahydrodibenz(a,j)acridine was assigned by conversion to the bis(p-(dimethylamino)benzoate) and examination of the exciton coupling in its circular dichroic (CD) spectrum. The 3(R),4(R)-tetrahydrodiol was converted to DBAJAC-3(R),4(R)-DHD. The enantiomers of DBAJAC 5,6-oxide were partially resolved by chiral stationary-phase chromatography, and subsequent methoxide attack afforded two enantiomerically enriched isomeric ethers from each fraction. The structures of the two ethers from each enantiomer were determined, and from their {sup 1}H NMR spin-spin coupling between the H{sub 5} and H{sub 6} signals and the CD spectra of the ethers, the absolute configuration of the ethers, and hence the 5,6-oxides, was determined. The enantiomeric composition of the 3,4-dihydrodiol and 5,6-oxide formed as microsomal metabolites of rat liver preparations was 69% 3R,4R and 81% 5R,6S, respectively.

• OSTI ID: 5182425
• Journal Information: Chemical Research in Toxicology; (USA), Journal Name: Chemical Research in Toxicology; (USA) Vol. 1:5; ISSN CRTOE; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACRIDINES
ANIMALS
AROMATICS
AZAARENES
AZINES
BODY
CARCINOGEN SCREENING
CELL CONSTITUENTS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
GLANDS
HETEROCYCLIC COMPOUNDS
LIVER
MAMMALS
METABOLISM
METABOLITES
MICROSOMES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PYRIDINES
RATS
RIBOSOMES
RODENTS
SCREENING
SEPARATION PROCESSES
STEREOCHEMISTRY
VERTEBRATES