Effect of Bay Region Methyl Group on Reactions of anti-Benzanthracene 3,4-Dihydrodiol 1,2-Epoxides with DNA

Article abstract of DOI:10.1021/jo00013a020

The NMR spectroscopic characterization of seven 7-methylbenzanthracene-deoxyribonucleoside adducts and eight 7,12-dimethylbenzanthracene-deoxyribonucleoside adducts, derived from the reaction of the corresponding anti-dihydrodiol epoxides and deoxyguanylic and deoxyadenylic acids, is described.The epoxide ring is opened by the purine amino groups to yield both cis and trans products from each enantiomer in the racemic dihydrodiol epoxides.Circular dichroism and NMR spectra allow the conformations of the products to be established.Interesting differences betweeen the products from the two hydrocarbons are as follows: the dimethyl derivative is distributed fairly evenly over adenine and guanine residue in DNA, whereas guanine is the principal site for reaction of the monomethyl derivative; the conformation of the tetrahydro ring system is similar in trans products for both hydrocarbons with the hydrogens on C3 and C4 being pseudodiaxial; in cis adducts, these hydrogens are pseudodiaxial for 7,12-dimethylbenzanthracene adducts but pseudodiequatorial for the 7-methylbenzanthracene adducts; in reactions with nucleotides, trans adducts predominate for 7-methylbenzanthracene derivatives but trans and cis adducts form to similar extents for 7,12-dimethylbenzanthracene derivatives.This latter differs substantially from previous findings with other bay region substituted hydrocarbons where cis adducts have been obtained only in low yields.