Chemical synthesis of the 3-sulfooxy-7-N-acetylglucosaminyl-24-amidated conjugates of 3β,7β-dihydroxy-5-cholen-24-oic acid, and related compounds:: Unusual, major metabolites of bile acid in a patient with Niemann-Pick disease type C1
Chemical synthesis of the 3-sulfooxy-7-N-acetylglucosaminyl-24-amidated conjugates of 3β,7β-dihydroxy-5-cholen-24-oic acid, and related compounds:: Unusual, major metabolites of bile acid in a patient with Niemann-Pick disease type C1
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DOI：
10.1016/j.steroids.2005.07.008
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发表时间：
2006-01-01
期刊：
影响因子：
2.7
通讯作者：
Hofmann, AF
中科院分区：
文献类型：
--
作者：
Iida, T;Kakiyama, G;Hofmann, AF
描述了3 β，7 β-二羟基-S-胆烯-24-酸的化学合成，该3 β，7 β-二羟基-S-胆烯-24-酸在C-3处通过硫酸、在C-7处通过N-乙酰葡糖胺（GlcNAc）和在C-24处通过甘氨酸或牛磺酸三重共轭。这些是发现在C1型尼曼-匹克病患者尿液中排泄的胆汁酸的不寻常的主要代谢物。还制备了3 β-羟基-7-氧代-5-胆烯-24-酸的类似双缀合物。主要反应为：（1）3 β-叔丁基二甲基硅氧基（TBDMSi）-7 β-羟基-5-胆烯-24-酸甲酯与2-乙酰氨基-1 α-氯-1，2-二脱氧-3，4，6-三-O-乙酰基-D-吡喃葡萄糖在CdCO_3存在下在沸腾甲苯中的C-7位进行β-D-N-乙酰氨基葡萄糖化;（2）在吡啶中用三氧化硫-三甲基胺络合物在C-3处硫酸化所得3 β-TBDMSi-7 β-GlcNAc;和（3）用甘氨酸甲酯盐酸盐在3 β-磺氧基-7 β-GlcNAc缀合物的C-24处直接酰胺化在DMF中使用4-（4，6-二甲氧基-1，3，5-三嗪-2-基）-4-甲基吗啉鎓氯化物作为偶联剂，通过将所述化合物（或牛磺酸）与所述化合物（或牛磺酸）反应来制备。多结合胆汁酸的结构进行了表征，通过液相色谱-质谱与电喷雾离子化探针的正负离子模式。(c)2005年爱思唯尔公司All rights reserved.
The chemical synthesis of 3 beta,7 beta-dihydroxy-S-cholen-24-oic acid, triply conjugated by sulfuric acid at C-3, by N-acetylglucosamine (GlcNAc) at C-7, and by glycine or taurine at C-24, is described. These are unusual, major metabolites of bile acid found to be excreted in the urine of a patient with Niemann-Pick disease type C1. Analogous double - conjugates of 3 beta-hydroxy-7-oxo-5-cholen-24-oic acid were also prepared. The principal reactions involved were: (1) beta-D-N-acetylglucosaminidation at C-7 of methyl 3 beta-tert-butyldimethylsilyloxy (TBDMSi)-7 beta-hydroxy-5-cholen-24-oate with 2-acetamido-1 alpha-chloro-1,2-dideoxy-3,4,6-tri-O-acetyl-D-glucopyranose in the presence of CdCO3 in boiling toluene; (2) sulfation at C-3 of the resulting 3 beta-TBDMSi-7 beta-GlcNAc with sulfur trioxide-trimethylamine complex in pyridine; and (3) direct amidation at C-24 of the 3 beta-sulfooxy-7 beta-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 an electrospray ionization probe under the positive and negative ionization modes. (c) 2005 Elsevier Inc. All rights reserved.