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.

介绍了一种高效合成胆汁酸羧基连接糖苷的方法。以2-氯-1，3，5-三硝基苯为偶联剂，将无保护胆汁酸与2，3，4，6-四-O-苯基-D-吡喃葡萄糖在吡啶中直接酯化，得到胆汁酸1-O-酰基-D-葡萄糖苷苄基醚的α-和β-异构体的混合物(约1：4)，经C&lt；18&gT；反相色谱分离。在10%Pd/C催化剂上，α-和β-酰基糖苷苯甲醚在常压下氢解得到相应的游离酯。建立了以甲基β-环糊精或离子对高效液相色谱为流动相添加剂，分离胆酸酯糖苷不同系列离子、高极性和亲水性结合物混合物的方法。工业高效液相色谱法和离子对高效液相色谱法均获得了较好的分离效果和柱性能。本方法为生物重要的胆汁酸酯糖苷的分离和结构鉴定提供了一种新的方法。

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)