Development of the Detection and Measurement of Bile Acid Ester Glycosides as Markers of Liver Diseases in Humans

作为人类肝脏疾病标志物的胆汁酸酯糖苷的检测和测量的进展

• 批准号: 10640597
• 负责人: IIDA Takashi
• 金额: $ 0.58万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10640597/
• 关键词: Steroid; Bile acid; Unusual bile acid; Hepatobiliary disease; Bile acid ester glycoside; Acyl glycoside; 2-Chloro-1,3,5-trinitrobenzene; 肝疾患マーカー; 胆汁酸エステルグルコシド; 胆汁酸アシルグルコシド; 胆汁酸グリコシド; 高速液体クロマトグラフィー

An efficient synthesis of the carboxyl-linked glucosides of bile acids was described. Direct esterification of unprotected bile acids with 2,3,4,6-tetra-O-benzyl-D-glucopyranose in pyridine in the presence of 2-chloro-1,3,5-trinitrobenzene as a coupling agent afforded a mixture of the α- and β-anomers (ca. 1 : 4) of the 1-O-acyl-D-glucoside benzyl ethers of bile acids, which was effectively separated on a C_<18> reversed-phase chromatography. Subsequent hydrogenolysis of the α- and β-acyl glucoside benzyl ethers on a 10% Pd/C catalyst at atomospheric pressure gave the corresponding free esters. A facile hydrolysis and transesterification of the acyl glucosides in various solvents were also revealed.A method for the separation of a mixture of different series of ionic, high polar, and hydrophilic conjugates of bile acid ester glucosides by indusion high performance liquid chromatography (HPLC) with methyl β-cyclodextrin or by ion-pair HPLC with an ion-pair chromatographic reagent, di-n-butylamine acetate (DBAA), as mobile phase additives. Satisfactory chromatographic separation and column performance were attained by the indusion HPLC and ion-pair HPLC methods. The present methods provide an insight into the separation and structural elucidation of biologically important bile acid ester glucosides.

描述了胆汁酸的羧基连接糖苷的有效合成。在2-氯-1,3,5-三硝基苯存在的情况下，用2,3,4,6,-o-o-benzyl-d-葡萄糖酰糖直接酯化未受保护胆汁酸，在C_ <18>相反相色谱上有效分离。随后在10％Pd/c催化剂在阳性压力下，α-和β-酰基葡萄糖二苯甲酸乙二醇的氢解会产生相应的游离酯。还揭示了各种溶液中酰基糖苷的便捷水解和酯交酯化。 Di-N-丁胺乙酸（DBAA）作为流动相添加剂。通过输注HPLC和离子对HPLC方法连接了令人满意的色谱分离和色谱柱性能。目前的方法提供了对生物学上重要的胆汁酸酯糖苷的分离和结构阐明的见解。

项目成果

飯田隆: "ライフサイエンス 有機化学"共立出版(株). 224 (2000)

饭田隆：《生命科学有机化学》共立出版社224（2000）

T.Momose: "Structure-Retention Correlation of Iscmeric Bile Acids in Inclusion High-Performance Liquid Chromatography…" Lipids. Vol.33 No.1. 101-108 (1998)

T.Momose：“包涵体高效液相色谱中异构胆汁酸的结构保留相关性……”脂质，第 33 卷第 101-108 期。

T.Momose, et al.: "Simultaneous Analysis and Retention Behavior of the Glucuronide, Glucoside, and N-Acetylglucosaminide Conjugates of Bile Acids・・・・・・・"J.Chromatogr. A. 803. 121-129 (1998)

T.Momose 等人：“胆汁酸的葡萄糖醛酸、葡萄糖苷和 N-乙酰氨基葡萄糖结合物的同时分析和保留行为……”J.Chromatogr. A. 803. 121-129 (1998)

飯田隆: "Separation of Double Conjugates of Bile Acids by Two-Dimensional High-Performance Thin-Layer Chromatography with Tetra-n-butylammonium Phosphate and Methyl β-Cyclodextrin"CHROMATOGRAPHIA. 49. 681-685 (1999)

Takashi Iida：“使用四正丁基磷酸铵和甲基 β-环糊精进行二维高效薄层色谱法分离胆汁酸的双重结合物”CHROMATOGRAPHIA 49. 681-685 (1999)。

T.Momose, et al.: "Structure-Retention Correlation of Isomeric Bile Acids in Inclusion High Performance. Liquid Chromatography with Methyl β-Cyclodextrin."Lipids. 33. 101-108 (1998)

T.Momose 等人：“内含物中同分异构胆汁酸的结构保留相关性。甲基 β-环糊精液相色谱法。”脂质。33. 101-108 (1998)