Synthesis, stereochemistry and reactivity of the highly mutagenic bay-region diol epoxides from benzo(c)phenanthrene

Conference · Fri Aug 01 04:00:00 EDT 1980 · Am. Chem. Soc., Div. Pet. Chem., Prepr.; (United States)

OSTI ID:5011690

Sayer, J M; Yagi, H; Croisy-Delcey, M; Jerina, D M

Within the past six years, epoxides on saturated benzo-rings in which the epoxide group forms part of a sterically hindered bay-region of the polycyclic aromatic hydrocarbon molecule have been identified as ultimate carcinogenic metabolites of a number of hydrocarbons. Several of these observations led to the formulation of the bay-region theory, which predicts that bay-region epoxides which yield stable benzylic carbonium ions (as indicated by large values of ..delta..E/sub deloc/..beta.. is for the formation of these carbonium ions) will be active as tumorigens and/or mutagens when derived from carcinogenic hydrocarbons. This prediction is in good qualitative agreement with the decreasing order of tumorigenicity and mutagenicity for the biologically active diastereomers of the bay-region diol eoxides derived from benzo(a)pyrene, benzo(a)anthracene and its derivatives, and chrysene. Factors, in addition to carbonium ion stability, also play an essential role in determining the chemical and biological activity of these molecules; namely, S/sub N/2 reactivity, steric, stereoelectronic and conformational effects, hydrogen bonding, size, shape and hydrophobic character of the aromatic moiety, and possible complexation effects with biological macromolecules. As part of studies to assess the importance of these factors, we have investigated the diastereomeric diol epoxides (+)-3..cap alpha.., 4..beta..-dihydroxy-1..beta.., 2..beta..-epoxy-1,2,3,4,-tetrahydrobenzo(c)phenanthrene, 1 and (+)-3..cap alpha.., 4..beta..-dihydroxy-1..cap alpha.., 2..cap alpha..-epoxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene, 2.

• Research Organization: National Inst. of Health, Bethesda, MD
• OSTI ID: 5011690
• Report Number(s): CONF-800814-P1
• Conference Information: Journal Name: Am. Chem. Soc., Div. Pet. Chem., Prepr.; (United States) Journal Volume: 25:3
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400301* -- Organic Chemistry-- Chemical & Physicochemical Properties-- (-1987)
AROMATICS
BENZENE
CONDENSED AROMATICS
EPOXIDES
HYDROCARBONS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHENANTHRENE
STEREOCHEMISTRY
SYNTHESIS