The trans-cis isomerization of trans-4'-(2-hydroxy-3,5-dibromo-benzylamino)cyclohexanol in vivo and in vitro in different species.

Isomerization of trans-4'-(2-hydroxy-3,5-dibromo-benzylamino)cyclohexanol (HDBC) in vivo has been investigated in horse, cow, dog, rat and man. Following oral administration of 4'-trans-HDBC to the horse, a very efficient first-pass trans-cis isomerization was observed. In the urine of the horse and cow, 40% and 29% respectively of the conjugated alcohols consisted of the 4'-cis isomer. Isomerization in rat and dog took place only to a small extent, and in man no 4'-cis isomer was detected. Oxidation of HDBC to the corresponding ketone, at pH 9.0, was highest with horse- and rat-liver 10 000 g supernatants and lowest with dog-liver supernatant. Reduction of the ketone with 10 000 g liver supernatants and with cryst. horse-liver alcohol dehydrogenase led to the formation of the alcohol containing 42-69% as the 4'-cis isomer, whereas after reduction with NaBH4 the alcohol contained only 20% of the 4'-cis isomer. This indicates that the conformer with the lower energy (1' and 4' position equatorially substituted) preferentially formed only during chemical reduction. A correlation between the formation of the ketone in vitro and the formation of 4'-cis-HDBC in vivo was observed in the horse, cow and dog. No similar correlation was found in the rat, where a high in vivo trans-cis isomerization might have been expected from the in vitro data.