Methylation and dehydroxylation of phenolic compounds by rats and rabbits.

It has been reported by Murray, Booth, DeEds, and Jones (1) that oral administration of rutin, or its aglycone quercetin, to rabbits results in the urinary excretion of 3,4-dihydroxyphenylacetic acid (DHPAA) . Subsequently, Booth et al. (2) showed that oral administration of these flavonoids also resulted in the excretion of 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid (HVA)) , and produced a marked increase in the amount of m-hydroxyphenylacetic acid (m-HPAA) which they found in small amount in normal rabbit urine. They also demonstrated that oral administration of DHPAA to both rabbits and rats resulted in the urinary excretion of HVA and m-HPAA. Methylation of hydroxyl group 3 of DHPAA would account for the formation of HVA, while removal of hydroxyl group 4 would yield m-HPAA. Lederer (3) stated in 1949 that “methylations of phenolic hydroxyl groups have not yet been observed in the animal organism,” but in 1951 Maclagan and Wilkinson (4) reported the methylation of a hydroxyaromatic compound in the human body. The ability of the animal body to introduce hydroxyl groups into the benzene ring is, of course, well known, but we are unaware of any investigations demonstrating the removal of a phenolic hydroxyl group.