Chemical synthesis, structural analysis, and decomposition of N-nitroso bile acid conjugates

✍ Scribed by Bishambar Dayal; Jalpa Bhojawala; Keshava R. Rapole; Birendra N. Pramanik; Norman H. Ertel; Sarah Shefer; Gerald Salen

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 655 KB
• Volume: 4
• Category: Article
• ISSN: 0968-0896
• DOI: 10.1016/0968-0896(96)00084-3

✦ Synopsis

N-nitrosoamides of 713-hydroxylated bile acid conjugates, particularly of the ursodeoxycholic acid family have been scnthesized. The products and synthetic intermediates were fully characterized by the results of high-resolution IH NMR, FT-IR, t'ABMS and ESI-MS studies. The compounds, N-nitrosoglycoursodeoxycholic acid (NOGUDCA), N-nitrosoglycoursocholic acid (NOGUCA) and N-nitrosoglycodeoxycholic acid (NOGDCA) decomposed between pH 6 and 9 in aqueous buffer solutions, iadicating a t,,2 of 5-7 h while N-nitrosotauroursodeoxycholic acid (NOTUDCA) indicated a much longer t~/2 of 15-17 h. These results suggest that the compounds are relatively stable and may enter the enterohepatic circulation. Their decomposition is similar to that of other N-nitrosamides, which generate alkylating agents and thereby act as DNA mutagens.