N-亚硝基胆汁酸共轭物的化学合成、结构分析及分解

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

作者信息

Dayal B, Bhojawala J, Rapole K R, Pramanik B N, Ertel N H, Shefer S, Salen G

机构信息

Medical Service, Veterans Administration Medical Center, East Orange, NJ 07019, USA.

出版信息

Bioorg Med Chem. 1996 Jun;4(6):885-90. doi: 10.1016/0968-0896(96)00084-3.

DOI:10.1016/0968-0896(96)00084-3

PMID:8818239

Abstract

N-nitrosoamides of 7 beta-hydroxylated bile acid conjugates, particularly of the ursodeoxycholic acid family have been synthesized. The products and synthetic intermediates were fully characterized by the results of high-resolution 1H NMR, FT-IR, FABMS 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, indicating a t1/2 of 5-7 h while N-nitrosotauroursodeoxycholic acid (NOTUDCA) indicated a much longer t1/2 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.

摘要

已合成了7β-羟基化胆汁酸缀合物的N-亚硝基酰胺，特别是熊去氧胆酸家族的此类化合物。通过高分辨率1H NMR、FT-IR、FABMS和ESI-MS研究结果对产物和合成中间体进行了全面表征。化合物N-亚硝基甘氨熊去氧胆酸（NOGUDCA）、N-亚硝基甘氨鹅去氧胆酸（NOGUCA）和N-亚硝基甘氨脱氧胆酸（NOGDCA）在水性缓冲溶液中于pH 6至9之间分解，表明半衰期为5 - 7小时，而N-亚硝基牛磺熊去氧胆酸（NOTUDCA）的半衰期则长得多，为15 - 17小时。这些结果表明这些化合物相对稳定，可能进入肠肝循环。它们的分解与其他N-亚硝基酰胺类似，后者会生成烷基化剂，从而作为DNA诱变剂起作用。