Reaction of Adenine with 6-Hydroxyestrogen 6-Sulfates : Model Compounds to Demonstrate Carcinogenesis by Estrogen

Abstract

To examine carcinogenesis by estrogens, we investigated the reactivity of 6-hydroxyestrogen 6-sulfates. Two epimeric 6-sulfates, pyridinium 3-methoxyestra-1, 3, 5(10)-trien-6α-yl sulfate (1) and its 6β-isomer (2), were synthesized as model compounds and reacted with adenine under mild conditions to give two common products in the ratios of approximately 3 : 1 and 5 : 1, respectively. The major product was identified as N⁶-[3-methoxyestra-1, 3, 5(10)-trien-6β-yl] adenine (10), accompanied with its 6α-isomer (9), by comparison with synthetic specimens. These results imply that, in the metabolism of naturally occurring estrogens, hydroxylation at the C₆-position and subsequent sulfoconjugation of the benzylic hydroxyl group may produce sulfates which react with DNA to initiate carcinogenesis.