[(3aR,5R,6S,7R,7aR)-6,7-diacetyloxy-2-(iodomethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazol-5-yl]methyl acetate | 944070-32-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(3aR,5R,6S,7R,7aR)-6,7-diacetyloxy-2-(iodomethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazol-5-yl]methyl acetate
• CAS: 944070-32-0
• 化学式: C₁₄H₁₈INO₇S
• 分子量: 471.27
• InChiKey: OQIOVXPVTRPIPR-DKTYCGPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  126
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(3aR,5R,6S,7R,7aR)-6,7-diacetyloxy-2-(iodomethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazol-5-yl]methyl acetate 在 甲醇 、 sodium azide 、 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 (3aR,5R,6S,7R,7aR)-2-(azidomethyl)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol
  参考文献：
  名称：

  Tautomeric Modification of GlcNAc-Thiazoline

  摘要：

  The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by buffer- or acylation-induced imine-to-enamine conversion and then electrophile or radical addition (X-n = D-3, F, N-3, OH, SMe, COCF3, CF3). Several functionalized GlcNAc-thiazolines show highly selective inhibition of OGA vs human hexosaminidase and thus have promise as tools for targeted investigations of OGA, an enzyme linked to diabetes and neurodegeneration. A new radical addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been discovered.

  DOI：

  10.1021/ol0706814
• 作为产物：
  描述：

  (3aR,5R,6S,7R,7aR)-5-(acetoxymethyl)-6,7-diacetoxy-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole 在 吡啶 、 三氟甲磺酸 、 碘 作用下， 以 乙腈 为溶剂， 以60%的产率得到[(3aR,5R,6S,7R,7aR)-6,7-diacetyloxy-2-(iodomethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazol-5-yl]methyl acetate
  参考文献：
  名称：

  Tautomeric Modification of GlcNAc-Thiazoline

  摘要：

  The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by buffer- or acylation-induced imine-to-enamine conversion and then electrophile or radical addition (X-n = D-3, F, N-3, OH, SMe, COCF3, CF3). Several functionalized GlcNAc-thiazolines show highly selective inhibition of OGA vs human hexosaminidase and thus have promise as tools for targeted investigations of OGA, an enzyme linked to diabetes and neurodegeneration. A new radical addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been discovered.

  DOI：

  10.1021/ol0706814

文献信息

• Synthesis of NAG-thiazoline-derived inhibitors for β-N-acetyl-d-hexosaminidases
  作者：Hanchu Kong、Wei Chen、Huizhe Lu、Qing Yang、Yanhong Dong、Daoquan Wang、Jianjun Zhang

  DOI：10.1016/j.carres.2015.06.004

  日期：2015.9

  beta-N-Acetyl-D-hexosaminidases are responsible for the metabolism of glycoconjugates in diverse physiological processes that are important targets for medicine and pesticide development. Fourteen new NAG-thiazoline derivatives were synthesized by cyclization and click reaction using D-glucosamine hydrochloride as the starting material. All the compounds created were characterized by NMR and HRMS spectra. A preliminary bioassay, using four enzymes from two beta-N-acetyl-D-hexosaminidase families, showed that most of the compounds synthesized exhibit selective inhibition of GH84 beta-N-acetyl-D-hexosaminidase. Among the compounds tested, compounds 5a (IC50 = 12.6 mu M, hOGA) and 5e (IC50 = 12.5 mu M, OfOGA) proved to be a highly selective and potent inhibitor. (C) 2015 Elsevier Ltd. All rights reserved.