Determination and measurement of unusual metabolites of bile acid multi-conjugates excreted in a patient with Nimann-Pick disease type C1.

测定和测量 C1 型尼曼-匹克病患者排出的胆汁酸多结合物的异常代谢物。

• 批准号: 15510182
• 负责人: IIDA Takashi
• 金额: $ 2.24万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15510182/
• 关键词: unsaturated bile acid; unusual bile acid conjugate; aminoacylamidation; sulfation; N-acetylglucosamidation; liver disease; tandem mass spectrometry; electrospray ionization mass spectrometry; 異常胆汁酸; 3β,7β-ジヒドロキシ-5-コレン酸; 胆汁酸多重抱合体; 3-スルフェート抱合体

The chemical synthesis of 3β,7β-dihydroxy-5-cholen-24-oic acid triply conjugated by sulfuric acid at C-3,N-acetylglucosamine (GlcNAc) at C-7 and glycine (or taurine) at C-24, which are unusual, major metabolites excreted in urine of a patient with Niemann-Pick diseases type C1,is described. Analogous double-conjugates of 3β-hydroxy-7-oxo-5-cholen-24-oic acid were also prepared. The principal reactions involved were : 1)β-D-N-acetylglueosaminidation at C-7 of methyl 3β-tert-butyldimethylsilyloxy (TBDMSi)-7β-hydroxy-5-cholen-24-oate with 2-acetamido-1α-chloro-1,2-dideoxy-3,4,6-tri-O-acetyl-D-glucopyranose in the presence of CdCO_3 in boiling toluene, 2)sulfation at C-3 of the resulting 3β-TBDMSi-7β-GlcNAc with sulfur trioxide-trimethylamine complex in pyridine, and 3)direct aminoacyl amidation at C-24 of the 3β-sulfo-7β-GlcNAc conjugate with glycine methyl ester hydrochloride (or taurine) using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as a coupling agent in DMF. The structures of the multi-conjugated bile acids were characterized by liquid chromatography-mass spectrometry with electrospray ionization probe under the positive and the negative ionization modes.

化学合成 3β,7β-二羟基-5-胆烯-24-oic 酸，由 C-7 处的 C-3,N-乙酰葡糖胺 (GlcNAc) 和 C-24 处的甘氨酸（或牛磺酸）三重结合，是不寻常的，主要代谢物在患有 C1 型尼曼-皮克病的患者的尿液中排泄，描述了类似的双缀合物。还制备了3β-羟基-7-氧代-5-cholen-24-oic酸，所涉及的主要反应是： 1)甲基3β-叔丁基二甲基甲硅烷氧基(TBDMSi)-7β-的C-7处的β-D-N-乙酰氨基葡萄糖化。羟基-5-胆-24-燕麦酸酯2-乙酰氨基-1α-氯-1,2-二脱氧-3,4,6-三-O-乙酰基-D-吡喃葡萄糖，在CdCO_3存在下，在沸腾的甲苯中，2)在C-3处硫酸化所得的3β- TBDMSi-7β-GlcNAc 与三氧化硫-三甲胺复合物在吡啶中，以及 3) 直接氨酰酰胺化使用 4-(4,6-二甲氧基-1,3,5-三嗪-2-基)-4-甲基吗啉氯化物作为 3β-磺基-7β-GlcNAc 与甘氨酸甲酯盐酸盐（或牛磺酸）缀合物的 C-24 DMF 中的偶联剂通过电喷雾液相色谱-质谱法表征了多结合胆汁酸的结构。电离探针在正电离和负电离模式下。

项目成果

飯田 隆: "A Comparative Study of Remote Oxy-functionalization of Unativated Carbons in 5β-Steroids by Dimethyldioxirane and 2,6-Dichloropyridine N-Oxide/Ruthenium Porphyrin/HBr."Arkivoc.. viii. 171-179 (2003)

Takashi Iida：“二甲基二环氧乙烷和 2,6-二氯吡啶 N-氧化物/钌卟啉/HBr 对 5β-类固醇中未活化碳的远程氧官能化的比较研究”Arkivoc.. viii。

An Improved Method for the Capillary Gas Chromatographic Derivatization of Polyhydroxylated Steroids Having tert.-Hydroxyl Groups.

具有叔羟基的多羟基类固醇的毛细管气相色谱衍生化的改进方法。

• 发表时间: 2003
• 期刊: Anal.Sci. 19(9)
• 作者: T.Iida;et al.
• 通讯作者: et al.

飯田 隆: "Functionalization of Unactivated Carbons in 3α,6- and 3α, 24-Dihydroxy-5β-cholane Derivatives by Dimethyldioxirane."Lipids. 38/3. 281-287 (2003)

Takashi Iida：“二甲基二环氧乙烷对 3α,6- 和 3α, 24-二羟基-5β-胆烷衍生物的功能化”38/3 (2003)。

飯田 隆: "An Improved Method for the Capillary Gas Chromatographic Derivatization of Polyhydroxylated Steroids Having tert.-Hydroxyl Groups."Anal.Sci.. 19/9. 1317-1321 (2003)

Takashi Iida：“具有叔羟基的多羟基类固醇的毛细管气相色谱衍生化的改进方法。”Anal.Sci. 19/9 (2003)。

飯田 隆(編著): "イラストで見る化学実験の基礎知識"丸善(株). 255 (2003)

饭田隆（编）：《通过插图了解化学实验的基础知识》Maruzen Co., Ltd. 255（2003）