(2R,3S,4R,5R,6R)-5-acetamido-2-(acetoxymethyl)-6-(tosylthio)tetrahydro-2H-pyran-3,4-diyl diacetate | 1020155-59-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3S,4R,5R,6R)-5-acetamido-2-(acetoxymethyl)-6-(tosylthio)tetrahydro-2H-pyran-3,4-diyl diacetate
• CAS: 1020155-59-2
• 化学式: C₂₁H₂₇NO₁₀S₂
• 分子量: 517.578
• InChiKey: HFBMALYCWIGBAM-PFAUGDHASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.07
• 重原子数：
  34.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  151.37
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R,5R,6R)-5-acetamido-2-(acetoxymethyl)-6-(tosylthio)tetrahydro-2H-pyran-3,4-diyl diacetate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.05h， 以98%的产率得到2-acetamido-2-deoxy-1-S-(4-methylbenzenesulfonyl)-1-thio-α-D-glucopyranose
  参考文献：
  名称：

  Distinctive Inhibition of O-GlcNAcase Isoforms by an α-GlcNAc Thiolsulfonate

  摘要：

  O-GlcNAcase (OGA) promotes O -GlcNAc removal, and thereby plays a key role in O-GlcNAc metabolism, a feature of a variety of vital cellular processes. Two splice transcripts of human OGA encode "long OGA", which contains a distinct N-terminal O -GlcNAcase domain and a C-terminal histoneacetylferase (HAT) domain, and "short OGA", which lacks the HAT domain. The functional roles of long OGA are only beginning to be unraveled, and the characteristics of short OGA remain almost unknown. We find that short OGA, which possesses O -GlcNAcase catalysis machinery like that of long OGA, exhibits comparative resistance to previously described potent inhibitors of long OGA and lysosomal hexosaminidases, including PUGNAc and NAG-thiazoline, suggesting a role for the HAT domain in O -GlcNAcase catalysis. We also find that alpha-GlcNAc thiolsulfonate (2) is the most potent inhibitor of short OGA yet described (K-i = 10 mu M), and exhibits some degree of selectivity versus long OGA and lysosomal hexosaminidases. In contrast to its mode of inhibition of short OGA, 2 acts as a irreversible inhibitor of long OGA by covalently modifying the enzyme as an S-GlcNAc derivative. Covalent attachment of GlcNAc to the HAT domain of long OGA dramatically changes its properties with respect to enzymatic activity and caspase-3 cleavage.

  DOI：

  10.1021/ja076038u
• 作为产物：
  描述：

  4-甲基苯磺酰溴 、 (2R,3S,4R,5R,6R)-5-acetamido-2-(acetoxymethyl)-6-mercaptotetrahydro-2H-pyran-3,4-diyl diacetate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以96%的产率得到(2R,3S,4R,5R,6R)-5-acetamido-2-(acetoxymethyl)-6-(tosylthio)tetrahydro-2H-pyran-3,4-diyl diacetate
  参考文献：
  名称：

  Distinctive Inhibition of O-GlcNAcase Isoforms by an α-GlcNAc Thiolsulfonate

  摘要：

  O-GlcNAcase (OGA) promotes O -GlcNAc removal, and thereby plays a key role in O-GlcNAc metabolism, a feature of a variety of vital cellular processes. Two splice transcripts of human OGA encode "long OGA", which contains a distinct N-terminal O -GlcNAcase domain and a C-terminal histoneacetylferase (HAT) domain, and "short OGA", which lacks the HAT domain. The functional roles of long OGA are only beginning to be unraveled, and the characteristics of short OGA remain almost unknown. We find that short OGA, which possesses O -GlcNAcase catalysis machinery like that of long OGA, exhibits comparative resistance to previously described potent inhibitors of long OGA and lysosomal hexosaminidases, including PUGNAc and NAG-thiazoline, suggesting a role for the HAT domain in O -GlcNAcase catalysis. We also find that alpha-GlcNAc thiolsulfonate (2) is the most potent inhibitor of short OGA yet described (K-i = 10 mu M), and exhibits some degree of selectivity versus long OGA and lysosomal hexosaminidases. In contrast to its mode of inhibition of short OGA, 2 acts as a irreversible inhibitor of long OGA by covalently modifying the enzyme as an S-GlcNAc derivative. Covalent attachment of GlcNAc to the HAT domain of long OGA dramatically changes its properties with respect to enzymatic activity and caspase-3 cleavage.

  DOI：

  10.1021/ja076038u