The Aristolochic Acids (AAs) are nephro- and geno-toxic substances of plant origin that have been found frequently as a constituent of medicinal herbs and in Balkan countries as a contaminant of wheat flour. They are cumulative toxins and relatively low doses induce irreversible disease in humans. Following our previously reported total syntheses of these nitrophenanthrenes and the AAII/DNA adducts , we have now applied the general methods to the synthesis of the dA-aristolactam I adduct, and the N-hydroxylactams of both AAI and AAII This sets the stage to identify the DNA adducts at very low levels in mammalian tissue and to resolve the ongoing polemic concerning the immediate precursors that lead to the so-called �ultimate carcinogens�, namely the nitrenium/carbenium ions that attack DNA. The results of solvolysis experiments with the N-hydroxylactams will be discussed.

Synthetic chemistry of the aristolochic acids, DNA adducts, and metabolic products: Comments on the mechanism(s) of DNA-adduct formation

244th National Meeting (2012)

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