Abstract
Isolated rat livers were perfused with 3,4-dimethoxybenzaldehyde and 3,4-dimethoxybenzoic acid, which were 14C-labelled in the m eta-and/or para-configurated methoxy group. Because the aldehyde group was completely oxydized to the carboxylic acid, the perfusions with 3,4-dimethoxybenzalde hyde and those with 3,4-dimethoxybenzoic acid exhibited principally the same results. After per fusion with a 1:1 mixture of (4 -O -[14C]methyl)-and (3 -O -[14C]methyl)-3,4-dimethoxybenzalde hyde, each of which had the same specific activity, thin layer chromatography of an extract of the perfusate revealed both radioactive 4-hydroxy-3-methoxybenzoic acid and radioactive 3-hydroxy-4-methoxybenzoic acid as demethylation products. The distribution of radioactivity between these two metabolites was determined as 20:1. Thus, demethylation of the 3,4-dimethoxyphenyl compound occurs preferentially at the para-configurated methoxy group. After perfusion with a mixture of (4-O-[14C] methyl) -and (3 -O -[14C] methyl) -3,4-dimethoxybenzoic acid under identical conditions the distribution of radioactivity of the named demethylation products was determined as 15:1.
After perfusion with (4 -O -[14C] methyl) -3,4-dimethoxybenzaldehyde or (4-O -[14C] methyl)-3,4-di-methoxybenzoic acid alone, extracts of the perfusates revealed the expected radioactive 3-hydroxy-4-methoxybenzoic acid. In addition it was found, that the 4-hydroxy-3-methoxybenzoic acid pro duced contained small quantities of radioactivity. From these results it may be infered that an interconversion between 3-hydroxy-4-methoxy-and 4-hydroxy-3-methoxybenzoic acid has occured. The identification of the metabolites, separated by thin-layer chromatography, was performed by the reversed isotope dilution technique
