The Formation in Vitro of (i- ) -Stercobilin from Bilk&in*

Stercobilin was first isolated from feces in 1932 (l), and it was soon observed to differ from the crystalline urobilin prepared from mesobilirubinogen (2, 3). This urobilin is optically inactive, hence designated as i-urobilin, in contrast to stercobilin, which was shown by Fischer, Halbach, and Stern, (4, 5) to be levorotatory. Fischer and Halbach also demonstrated a formal relationship of I-stercobilin to the 1X-a bile pigments (5) by virtue of its oxidation to glaucobilin, which in turn could be reduced to mesobilirubinogen. Although both the latter and i-urobilin yield methylethylmaleimide on CrOa oxidation, stercobilin does not (2, 3). Gray and Nicholson (6) have shown more recently that stercobilin, on CrOs oxidation, yields methylethylsuccinimide and hematinic acid; thus, Structure I (Fig. 1) is indicated for stercobilin hydrochloride. This structure may be contrasted with Structure II, for i-urobilin, as proven by Siedel and Meier’s synthesis (7), shown here in the bislactam form. Although when I-stercobilin is formed in the intestine by bacterial reduction of bilirubin, the addition of 6 moles of Hz is required, Fischer and Niemann (8) showed that an alkaline solution of bilirubin, in the presence of colloidal palladium at room temperature, took up only 4 moles of hydrogen to give the leuko compound mesobilirubinogen or i-urobilinogen, which is readily oxidized to the pigment i-urobilin (II). This report is in accord with recent findings (9) that 2-0x0As-pyrrolines are not readily hydrogenated under these conditions, and the present work was prompted by the observation (9) that these systems may be hydrogenated under more vigorous conditions.