Iida T, Nishida S, Yamaguchi Y, Kodake M, Chang F C, Niwa T, Goto J, Nambara T
College of Engineering, Nihon University, Fukushima, Japan.
J Lipid Res. 1995 Mar;36(3):628-38.
The 3-glucosides of nonamidated lithocholic, chenodeoxycholic, ursodeoxycholic, deoxycholic, and cholic acids, and their double conjugate forms with glycine and taurine were synthesized. The key reactions used were 1) beta-D- glucosidation at C-3 by the Koenigs-Knorr condensation reaction of 3 alpha-hydroxylated bile acid methyl (or p-nitrophenyl) esters with 1 alpha-bromo-1-deoxy-2, 3, 4, 6-tetra-O-acetyl-D-glucopyranose in the presence of cadmium carbonate in refluxing benzene; 2) indirect and direct amidations at C-24 by the activated p-nitrophenyl ester and by the diethylphosphorylcyanide methods, respectively, using glycinate ester and taurine as coupling agents; and 3) simultaneous alkaline hydrolysis of the hydroxyl-protecting and ester groups in both the sugar and aglycone moieties.
合成了未酰胺化的石胆酸、鹅去氧胆酸、熊去氧胆酸、脱氧胆酸和胆酸的3-葡萄糖苷，以及它们与甘氨酸和牛磺酸的双共轭形式。所采用的关键反应如下：1）在回流的苯中，在碳酸镉存在下，通过3α-羟基化胆汁酸甲酯（或对硝基苯基酯）与1α-溴-1-脱氧-2,3,4,6-四-O-乙酰基-D-吡喃葡萄糖的柯尼希斯-克诺尔缩合反应，在C-3位进行β-D-葡萄糖苷化；2）分别使用甘氨酸酯和牛磺酸作为偶联剂，通过活化的对硝基苯基酯法和二乙基磷酰氰法在C-24位进行间接和直接酰胺化；3）同时对糖部分和苷元部分的羟基保护基和酯基进行碱性水解。
