azidomethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-β-D-glucopyranoside | 669714-27-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: azidomethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-β-D-glucopyranoside
• 英文别名: azidomethyl 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-β-D-glucopyranoside；[(2R,3S,4R,5R,6S)-5-acetamido-3,4-diacetyloxy-6-(azidomethylsulfanyl)oxan-2-yl]methyl acetate
• CAS: 669714-27-6
• 化学式: C₁₅H₂₂N₄O₈S
• 分子量: 418.428
• InChiKey: PZEVWGJZBXDLIF-RYPNDVFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-(prop-2-yn-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione 、 azidomethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-β-D-glucopyranoside 在 氨 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 12.0h， 生成 2-[1-[(2-acetamido-β-D-glucopyranosylthiomethyl)-1H-1,2,3-triazol-4-yl]methyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  Selective inhibition of β-N-acetylhexosaminidases by thioglycosyl–naphthalimide hybrid molecules

  摘要：

  To develop selective inhibitors for beta-N-acetylhexosaminidases which are involved in a myriad of physiological processes, a series of novel thioglycosyl-naphthalimide hybrid inhibitors were designed, synthesized and evaluated for inhibition activity against glycosyl hydrolase family 20 and 84 (GH20 and GH84) beta-N-acetylhexosaminidases. These compounds which incorporate groups with varied sizes and lengths at the linker region between thioglycosyl moiety and naphthalimide moiety are designed to improve the selectivity and stacking interactions. The GH84 human O-GlcNAcase (hOGA) was sensitive to the subtle changes in the linker region and the optimal choice is a small size linker with six atoms length. And the GH20 insect beta-N-acetylhexosaminidase OfHex1 could tolerate compounds with a hydrophobic bulky linker. Especially, the compound 5c (hOGA, K-i = 3.46 mu M; OfHex1, K-i > 200 mu M) and the compound 6f (hOGA, K-i > 200 mu M; OfHex1, K-i = 21.81 mu M) displayed high selectivity. The molecular docking results indicated that the inhibition mechanism was different between the two families due to their different structural characteristics beyond the active sites. These results provide some promising clues to improve selectivity of potent molecules against beta-N-acetylhexosaminidases. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.11.042
• 作为产物：
  描述：

  chloromethyl 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-β-D-glucopyranoside 在 sodium azide 作用下， 以 水 、 丙酮 为溶剂， 生成 azidomethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Selective inhibition of β-N-acetylhexosaminidases by thioglycosyl–naphthalimide hybrid molecules

  摘要：

  To develop selective inhibitors for beta-N-acetylhexosaminidases which are involved in a myriad of physiological processes, a series of novel thioglycosyl-naphthalimide hybrid inhibitors were designed, synthesized and evaluated for inhibition activity against glycosyl hydrolase family 20 and 84 (GH20 and GH84) beta-N-acetylhexosaminidases. These compounds which incorporate groups with varied sizes and lengths at the linker region between thioglycosyl moiety and naphthalimide moiety are designed to improve the selectivity and stacking interactions. The GH84 human O-GlcNAcase (hOGA) was sensitive to the subtle changes in the linker region and the optimal choice is a small size linker with six atoms length. And the GH20 insect beta-N-acetylhexosaminidase OfHex1 could tolerate compounds with a hydrophobic bulky linker. Especially, the compound 5c (hOGA, K-i = 3.46 mu M; OfHex1, K-i > 200 mu M) and the compound 6f (hOGA, K-i > 200 mu M; OfHex1, K-i = 21.81 mu M) displayed high selectivity. The molecular docking results indicated that the inhibition mechanism was different between the two families due to their different structural characteristics beyond the active sites. These results provide some promising clues to improve selectivity of potent molecules against beta-N-acetylhexosaminidases. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.11.042

文献信息

• Glycosylthiomethyl Chloride:  A New Species for <i>S</i>-Neoglycoconjugate Synthesis. Synthesis of 1-<i>N</i>-Glycosylthiomethyl-1,2,3-triazoles
  作者：Xiangming Zhu、Richard R. Schmidt

  DOI：10.1021/jo035300o

  日期：2004.2.1

  Reaction of O-acyl-protected glycosylthiols with dichloromethane afforded readily glycosylthiomethyl chlorides, which gave with sodium azide the corresponding glycosylthiomethyl azides 17-22. Reaction of these azides with dicyclopentadiene as dipolarophile led to tandem 1,3-dipolar cycloaddition/retro-Diels-Alder reaction furnishing the parent 1-glycosylthiomethyl-1,2,3-triazoles 23-25. Reaction of azides with acetylene derivatives gave directly 1-glycosylthiomethyl-1,2,3-triazoles which are ring-substituted.