2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-1-C-sulfonamide | 1138026-28-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-1-C-sulfonamide
• 英文别名: 1-S-(2,3,4,6-tetra-O-acetyl)-D-glucopyranosylsulfonamide；[(2R,3R,4S,5R,6S)-3,4,5-triacetyloxy-6-sulfamoyloxan-2-yl]methyl acetate
• CAS: 1138026-28-4
• 化学式: C₁₄H₂₁NO₁₁S
• 分子量: 411.387
• InChiKey: KEPSAHFFASUILI-RGDJUOJXSA-N

物化性质

• 熔点：
  201-204 °C
• 沸点：
  516.5±60.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  183
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-1-C-sulfonamide 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 β-D-glucopyranosyl-1-C-sulfonamide
  参考文献：
  名称：

  S-Glycosyl Primary Sulfonamides−A New Structural Class for Selective Inhibition of Cancer-Associated Carbonic Anhydrases

  摘要：

  In this paper, we present. a. new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is absent from these compounds and instead they incorporate a hydrophilic mono- or disaccharide fragment directly attached to the sulfonamide group to give S-glycosyl primary sulfonamides (1-10). The inhibition properties of these compounds at the physiologically abundant human CA isozymes I and II and cancer-associated IX and XII were determined, and all compounds had moderate potency with KiS in the micromolar range. We present the crystal structures of anomeric sulfonamides 4, 7, and 10 and the sugar sulfamate drug topiramate in complex with human recombinant CA II. From these structures, we have obtained valuable insights into ligand-protein interactions of these novel carb ohydrate-based sulfonamides with CA.

  DOI：

  10.1021/jm900914e
• 作为产物：
  描述：

  (2S,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxane-2-sulfinate 在 sodium acetate 、 hydroxylamine-O-sulfonic acid 作用下， 以 水 为溶剂， 反应 2.0h， 以81%的产率得到2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-1-C-sulfonamide
  参考文献：
  名称：

  Synthesis of anomeric sulfonamides and their behaviour under radical-mediated bromination conditions

  摘要：

  O-Peracetylated methyl 3-(D-glycopyranosylthio)propanoates of beta-D-gluco, and alpha- and beta-D-galacto configurations were oxidized to the corresponding S,S-dioxides (sulfones) by Oxone (R) or MCPBA. Oxidation of the beta-D-gluco derivative with H2O2/Na2WO4 gave the corresponding S-oxide (sulfoxide). DBU-induced elimination of methyl acrylate from the P-D-gluco and P-D-galacto configured SS-dioxides (sulfones) gave O-peracetylated beta-D-glycopyranosyl-1-C-sulfinates which, on treatment with H2NOSO3H, furnished the corresponding beta-D-glycopyranosyl-1-C-sulfonamides. Radical-mediated bromination of the protected methyl 3-(beta-D-glycopyranosylthio)propanoate S.S-dioxides gave mixtures of 1-C- and 5-C-bromoglycosyl compounds. Similar brominations of the O-peracetylated beta-D-glycopyranosyl-1-C-sulfonamides resulted in the formation Of U-D-glycopyranosyl bromides and 1-C- and 5-C-bromoglycosyl sulfonamides. A rationale for these observations was proposed. Methyl 3-(beta-D-glucopyranosylthio)propanoate, its S,S-dioxide, and beta-D-glucopyranosyl-1-C-sulfonamide proved inefficient when tested as inhibitors of rabbit muscle glycogen phosphorylase b. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2008.11.002

文献信息

• <i>S</i>-Glycosyl Primary Sulfonamides−A New Structural Class for Selective Inhibition of Cancer-Associated Carbonic Anhydrases
  作者：Marie Lopez、Blessy Paul、Andreas Hofmann、Julia Morizzi、Quoc K. Wu、Susan A. Charman、Alessio Innocenti、Daniela Vullo、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/jm900914e

  日期：2009.10.22

  In this paper, we present. a. new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is absent from these compounds and instead they incorporate a hydrophilic mono- or disaccharide fragment directly attached to the sulfonamide group to give S-glycosyl primary sulfonamides (1-10). The inhibition properties of these compounds at the physiologically abundant human CA isozymes I and II and cancer-associated IX and XII were determined, and all compounds had moderate potency with KiS in the micromolar range. We present the crystal structures of anomeric sulfonamides 4, 7, and 10 and the sugar sulfamate drug topiramate in complex with human recombinant CA II. From these structures, we have obtained valuable insights into ligand-protein interactions of these novel carb ohydrate-based sulfonamides with CA.
• Synthesis of <i>S</i>-Glycosyl Primary Sulfonamides
  作者：Marie Lopez、Nicolas Drillaud、Laurent F. Bornaghi、Sally-Ann Poulsen

  DOI：10.1021/jo9000367

  日期：2009.4.3

  The synthesis of S-glycosyl sulfonamides wherein the primary sulfonamide functional group (-SO2NH2) is directly attached to the anomeric position of a carbohydrate moiety is reported. Our general approach consists of first introducing a thioacetate group at die anomeric center of a per-O-acetylated sugar derivative. From this follows formation of a glycosyl sulfenamide (sugar-SNR2), oxidation of the sulfenamide to give a glycosyl N-protected sulfonamide (sugar-SO2NR2), and removal of the sulfonamide protecting (R) group to yield a primary sulfonamide at the anomeric center (sugar-SO2NH2). A variety of mono- and disaccharide derivatives were synthesized using this new methodology.
• Synthesis of anomeric sulfonamides and their behaviour under radical-mediated bromination conditions
  作者：Katalin Czifrák、László Somsák

  DOI：10.1016/j.carres.2008.11.002

  日期：2009.2

  O-Peracetylated methyl 3-(D-glycopyranosylthio)propanoates of beta-D-gluco, and alpha- and beta-D-galacto configurations were oxidized to the corresponding S,S-dioxides (sulfones) by Oxone (R) or MCPBA. Oxidation of the beta-D-gluco derivative with H2O2/Na2WO4 gave the corresponding S-oxide (sulfoxide). DBU-induced elimination of methyl acrylate from the P-D-gluco and P-D-galacto configured SS-dioxides (sulfones) gave O-peracetylated beta-D-glycopyranosyl-1-C-sulfinates which, on treatment with H2NOSO3H, furnished the corresponding beta-D-glycopyranosyl-1-C-sulfonamides. Radical-mediated bromination of the protected methyl 3-(beta-D-glycopyranosylthio)propanoate S.S-dioxides gave mixtures of 1-C- and 5-C-bromoglycosyl compounds. Similar brominations of the O-peracetylated beta-D-glycopyranosyl-1-C-sulfonamides resulted in the formation Of U-D-glycopyranosyl bromides and 1-C- and 5-C-bromoglycosyl sulfonamides. A rationale for these observations was proposed. Methyl 3-(beta-D-glucopyranosylthio)propanoate, its S,S-dioxide, and beta-D-glucopyranosyl-1-C-sulfonamide proved inefficient when tested as inhibitors of rabbit muscle glycogen phosphorylase b. (C) 2008 Elsevier Ltd. All rights reserved.