Glucuronides of the Mononitrophenols and Observations on the Anomalous Optical Rotations of Triacetyl

As a result of the discovery that nitro compounds occur in nature there is likely to be a renewed interest in their fate in the body. The antibiotic chloromycetin (chloramphenicol) has been shown to be a p-substituted nitrobenzene, and the plant glycosides, hiptagin and karakin, have been shown by Carter & McChesney (1949) to contain ,B-nitropropionic acid (hiptagenic acid). It is possible that the toxicity and perhaps the physiological effects of nitro compounds are related *to the modifications which the nitro group may undergo in vivo. The work of Channon, Mills & Williams (1944) on the metabolism of 2:4:6-trinitrotoluene (TNT) has shown that the aromatic nitro group may be reduced in vivo to a hydroxylamino and then to an amino group, and it appears that the biological reduction of the nitro group follows the path, NO2-+NO-*NHOH-÷NH2. Evidence in support of this path has been obtained by Bueding & Jolliffe (1946) who showed that reduced coenzyme i plus purified Straub flavoprotein probably converts TNT to a nitroso compound, that xanthine oxidase can convert TNT to the hydroxylamine and that whole tissue (rat liver and diaphragm) is necessary to convert TNT to the amine. In some compounds, however, the nitro group may be relatively resistant to reduction in vivo, for Glazko, Wolf, Dill & Bratton (1949) have reported that little if any chloromycetin is reduced in man (see also Glazko, Dill & Rebstock, 1950). Our intention in the present workwas to study the extent of reduction of the three mononitrophenols and attempt to relate it to their orientation and to the fact that p-nitrophenol is much more toxic than the ortho-compound. Beutner & Block (1943) and Dietrich & Beutner (1946) have shown that o-nitrophenol is relatively non-toxic and is largely excreted by rabbits with its nitro group unaltered. We also wished to isolate and characterize the glucuronides of the nitrophenols as a preliminary to a study on the metabolism ofnitrobenzene. Furthermore, tetra acetyl , o nitrophenyl -D glucoside shows an anomalous positive optical rotation (Glaser & Wulwek, 1924; Montgomery, Richtmyer & Hudson, 1942), and we were desirous of finding out whether or not a similar rotation would be shown by the corresponding acetylated ,-glucuronide.