Coleman J P, Kirby L C, Klein R A
Department of Microbiology and Immunology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
J Lipid Res. 1995 Apr;36(4):901-10.
New analogs of amino acid-conjugated bile acids were synthesized in which the amide bond was reversed from its normal configuration. These structural isomers of the beta-alanyl conjugates of cholic acid and ursodeoxycholic acid were synthesized by reaction of succinic anhydride with the 24-nor-23-amine derivatives of cholic acid and ursodeoxycholic acid. The chemical and physical properties of these reverse amide conjugated bile acid analogs were compared with those of the normal glycine and beta-alanine conjugates. The reverse amide analogs comigrated with their isomeric beta-alanine conjugates during thin-layer chromatography using a variety of solvent systems. However, the isomeric pairs could be resolved by reversed-phase high performance liquid chromatography, with the reverse amides having greater retention times compared to the beta-alanine conjugates. Critical micelle concentrations, solubility of undissociated forms, and acid dissociation constants were similar for the isomeric pairs. Significant differences in melting points were observed, however, While the isomeric pairs showed no significant differences in sensitivity to base hydrolysis, the reverse amides were not hydrolyzed by the cholylglycine hydrolase from Clostridium perfringens, even after long incubation periods.
合成了氨基酸共轭胆汁酸的新类似物，其中酰胺键的构型与正常构型相反。通过琥珀酸酐与胆酸和熊去氧胆酸的24-降-23-胺衍生物反应，合成了胆酸和熊去氧胆酸的β-丙氨酸共轭物的这些结构异构体。将这些反向酰胺共轭胆汁酸类似物的化学和物理性质与正常甘氨酸和β-丙氨酸共轭物的性质进行了比较。在使用多种溶剂系统的薄层色谱中，反向酰胺类似物与其异构的β-丙氨酸共轭物一起迁移。然而，异构对可以通过反相高效液相色谱法分离，与β-丙氨酸共轭物相比，反向酰胺具有更长的保留时间。异构对的临界胶束浓度、未解离形式的溶解度和酸解离常数相似。然而，观察到熔点有显著差异。虽然异构对在对碱水解的敏感性上没有显著差异，但即使经过长时间孵育，反向酰胺也不会被产气荚膜梭菌的胆酰甘氨酸水解酶水解。
