[(3aS,5aR,7R,8aR,8bS)-7-(羟基甲基)-2,2,7-三甲基四氢-3aH-二[1,3]二氧杂环戊并[4,5-b:4',5'-d]吡喃-3a-基]甲基氨基磺酸 | 198215-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧吡喃
• 中文名称: [(3aS,5aR,7R,8aR,8bS)-7-(羟基甲基)-2,2,7-三甲基四氢-3aH-二[1,3]二氧杂环戊并[4,5-b:4',5'-d]吡喃-3a-基]甲基氨基磺酸
• 中文别名: 2-羟基乙基丙-2-烯酸酯异苯并呋喃-1,3-二酮甲基2-甲基丙-2-烯酸酯噁丙环-2-基甲基7,7-二甲基辛酸酯苯乙烯
• 英文名称: Sulfamic acid (3aS,5aR,7S,8aR,8bS)-7-hydroxymethyl-2,2,7-trimethyl-tetrahydro-bis[1,3]dioxolo[4,5-b;4',5'-d]pyran-3a-ylmethyl ester
• 英文别名: R-Hydroxy Topiramate；[(1R,2S,6S,9R,11S)-11-(hydroxymethyl)-4,4,11-trimethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.02,6]dodecan-6-yl]methyl sulfamate
• CAS: 198215-62-2
• 化学式: C₁₂H₂₁NO₉S
• 分子量: 355.366
• InChiKey: RWNDWLAEFHRSEG-FBHFSLSBSA-N

物化性质

• 熔点：
  110-112°C
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,3-O-(1-甲基亚乙基)-beta-D-吡喃果糖1-氨基磺酸酯 在 palladium on activated charcoal 硫酸 、 氢气 、 原甲酸三乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 48.0h， 生成 [(3aS,5aR,7R,8aR,8bS)-7-(羟基甲基)-2,2,7-三甲基四氢-3aH-二[1,3]二氧杂环戊并[4,5-b:4',5'-d]吡喃-3a-基]甲基氨基磺酸
  参考文献：
  名称：

  Synthesis of hydroxylated derivatives of topiramate, a novel antiepileptic drug based on d-fructose: Investigation of oxidative metabolites

  摘要：

  To corroborate the structures of two monohydroxylated metabolites of topiramate (1), we synthesized four monosaccharide derivatives from D-fructose: 4,5-O-[(1R*)- and 4,5-O-[(1S* )-1-hydroxymethylethylidene]-2,3-O-isopropylidene-beta-D-fructopyranose sulfamates (2a and 2b); 2,3-O-[(1R*)- and 2,3-O-[(1R*)-1-hydroxymethylethylidene]-4,5-O-isopropylidene-beta-D-fructopyranose sulfamates (3a and 3b). The route to 2a and 2b was brief and straightforward, while that to 3a and 3b was more involved. In the latter case, the D-fructose bis-acetal 10 was benzylated and converted to a monoacetal dibenzoate (14) (50% yield), which was then transacetalized to give a mixture of 4,5-dibenzoyl-2,3-O-[(1R*)- and 4,5-dibenzoyl-2,3-O-[(1S* )-1-benzyloxymethylethylidene]-beta-D-fructopyranose (16a and 16b) (22%). The individual diastereomers were separated and processed via ester saponification, acetonation, sulfamoylation, and hydrogenolysis into 3a (36%) and 3b (27%). Structure 2b was confirmed for one oxidative metabolite, but the other metabolite was found not to correspond with either 2a, 3a, or 3b. On the basis of CI-MS and H-1 NMR data, a (2-hydroxy-1,4-dioxano)pyran structure, 4, is proposed for this unidentified metabolite. (C) 1997 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0008-6215(97)00214-0

文献信息

• Synthesis of hydroxylated derivatives of topiramate, a novel antiepileptic drug based on d-fructose: Investigation of oxidative metabolites
  作者：Samuel O. Nortey、Wu-Nan Wu、Bruce E. Maryanoff

  DOI：10.1016/s0008-6215(97)00214-0

  日期：1997.10

  To corroborate the structures of two monohydroxylated metabolites of topiramate (1), we synthesized four monosaccharide derivatives from D-fructose: 4,5-O-[(1R*)- and 4,5-O-[(1S* )-1-hydroxymethylethylidene]-2,3-O-isopropylidene-beta-D-fructopyranose sulfamates (2a and 2b); 2,3-O-[(1R*)- and 2,3-O-[(1R*)-1-hydroxymethylethylidene]-4,5-O-isopropylidene-beta-D-fructopyranose sulfamates (3a and 3b). The route to 2a and 2b was brief and straightforward, while that to 3a and 3b was more involved. In the latter case, the D-fructose bis-acetal 10 was benzylated and converted to a monoacetal dibenzoate (14) (50% yield), which was then transacetalized to give a mixture of 4,5-dibenzoyl-2,3-O-[(1R*)- and 4,5-dibenzoyl-2,3-O-[(1S* )-1-benzyloxymethylethylidene]-beta-D-fructopyranose (16a and 16b) (22%). The individual diastereomers were separated and processed via ester saponification, acetonation, sulfamoylation, and hydrogenolysis into 3a (36%) and 3b (27%). Structure 2b was confirmed for one oxidative metabolite, but the other metabolite was found not to correspond with either 2a, 3a, or 3b. On the basis of CI-MS and H-1 NMR data, a (2-hydroxy-1,4-dioxano)pyran structure, 4, is proposed for this unidentified metabolite. (C) 1997 Published by Elsevier Science Ltd.