3,4,5-Trimethoxycinnamic Acid and Related Compounds I. Metabolism by the Rat Intestinal Microflora

1. The metabolism of some substituted cinnamic and phenylpropionic acids by mixed cultures of rat caecal micro-organisms has been investigated. The compounds studied were: 3,4,5-trimethoxy-, 4-hydroxy-3,5-dimethoxy- and 3,5-dimethoxycinnamic acid, and 3,4,5-trimethoxy-, 3-hydroxy-4,5-dimethoxy-, 4-hydroxy-3,5-dimethoxy-, 3,4-dihydroxy-5-methoxy-, 3,5-dihydroxy-4-methoxy-, 3,4,5-trihydroxy-, 3,5-dimethoxy- and 3-hydroxy-5-methoxy-phenyl-propionic acid.

2. The metabolic reactions found to occur were hydrogenation of the double bond, O-demethylation and p-dehydroxylation. No decarboxylation was detected.

3. The ultimate metabolic product was 3,5-dihydroxyphenylpropionic acid which was formed from all of the trihydric derivatives.

4. The metabolic sequence from the trimethoxy derivatives to 3,5-dihydroxyphenylpropionic acid was not found to proceed along a single pathway. However, the major pathway appears to involve an initial meta-O-demethylation followed by para-O-demethylation and, then after the ultimate O-demethylation, p-dehydroxylation.