ethyl (2'R,3'R)-4,6-di-O-benzyl-2,3-di-O-(2',3'-dimethoxybutane-2',3'-diyl)-1-thio-β-D-glucopyranoside | 1357153-83-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl (2'R,3'R)-4,6-di-O-benzyl-2,3-di-O-(2',3'-dimethoxybutane-2',3'-diyl)-1-thio-β-D-glucopyranoside
• 英文别名: (2R,3R,4aR,5S,7R,8R,8aS)-5-ethylsulfanyl-2,3-dimethoxy-2,3-dimethyl-8-phenylmethoxy-7-(phenylmethoxymethyl)-5,7,8,8a-tetrahydro-4aH-pyrano[3,4-b][1,4]dioxine
• CAS: 1357153-83-3
• 化学式: C₂₈H₃₈O₇S
• 分子量: 518.672
• InChiKey: MMDIKMMXSGPRBC-XWOOICRWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  89.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (2'R,3'R)-4,6-di-O-benzyl-2,3-di-O-(2',3'-dimethoxybutane-2',3'-diyl)-1-thio-β-D-glucopyranoside 在 四丁基溴化铵 、 二正丁基氧化锡 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 25.0h， 生成 ethyl 3,4,6-tri-O-benzyl-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Contribution of Phosphates and Adenine to the Potency of Adenophostins at the IP₃ Receptor: Synthesis of All Possible Bisphosphates of Adenophostin A

  摘要：

  Although adenophostin A (AdA), the most potent agonist of D-myoinositol 1,4,5-trisphosphate receptors (IP3R), is thought to mimic IP3, the relative roles of the different phosphate groups and the adenosine motif have not been established. We synthesized all three possible bisphosphate analogues of AdA and glucose 3,4-bisphosphate (7, AdA lacking the 2'-AMP). 2'-Dephospho-AdA (6) was prepared via a novel regioselective dephosphorylation strategy. Assessment of the abilities of these bisphosphates to stimulate intracellular Ca2+ release using recombinant rat type 1 IP3R (IP(3)R1) revealed that 6, a mimic of Ins(4,5)P-2, is only 4-fold less potent than IP3, while 7 is some 400-fold weaker and even 3 ''-dephospho-AdA (5) is measurably active, despite missing one of the vicinal bisphosphate groups normally thought to be crucial for IP3-like activity. Compound 6 is the most potent bisphosphate yet discovered with activity at IP3R. Thus, adenosine has a direct role independent of the 2'-phosphate group in contributing toward the potency of adenophostins, the vicinal bisphosphate motif is not essential for activity at the IP3R, as always thought, and it is possible to design potent agonists with just two of the three phosphates. A model with a possible adenine-R504 interaction supports the activity of 5 and 6 and also allows a reappraisal of the unexpected activity previously reported for the AdA regioisomer 2 ''-phospho-3 ''-dephospho-AdA 40.

  DOI：

  10.1021/jm201571p
• 作为产物：
  描述：

  溴甲苯 、 (2'R,3'R)-ethyl 2,3-di-O-(2',3'-dimethoxybutane-2',3'-diyl)-1-thio-β-D-glucopyranoside 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.17h， 以100%的产率得到ethyl (2'R,3'R)-4,6-di-O-benzyl-2,3-di-O-(2',3'-dimethoxybutane-2',3'-diyl)-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Contribution of Phosphates and Adenine to the Potency of Adenophostins at the IP₃ Receptor: Synthesis of All Possible Bisphosphates of Adenophostin A

  摘要：

  Although adenophostin A (AdA), the most potent agonist of D-myoinositol 1,4,5-trisphosphate receptors (IP3R), is thought to mimic IP3, the relative roles of the different phosphate groups and the adenosine motif have not been established. We synthesized all three possible bisphosphate analogues of AdA and glucose 3,4-bisphosphate (7, AdA lacking the 2'-AMP). 2'-Dephospho-AdA (6) was prepared via a novel regioselective dephosphorylation strategy. Assessment of the abilities of these bisphosphates to stimulate intracellular Ca2+ release using recombinant rat type 1 IP3R (IP(3)R1) revealed that 6, a mimic of Ins(4,5)P-2, is only 4-fold less potent than IP3, while 7 is some 400-fold weaker and even 3 ''-dephospho-AdA (5) is measurably active, despite missing one of the vicinal bisphosphate groups normally thought to be crucial for IP3-like activity. Compound 6 is the most potent bisphosphate yet discovered with activity at IP3R. Thus, adenosine has a direct role independent of the 2'-phosphate group in contributing toward the potency of adenophostins, the vicinal bisphosphate motif is not essential for activity at the IP3R, as always thought, and it is possible to design potent agonists with just two of the three phosphates. A model with a possible adenine-R504 interaction supports the activity of 5 and 6 and also allows a reappraisal of the unexpected activity previously reported for the AdA regioisomer 2 ''-phospho-3 ''-dephospho-AdA 40.

  DOI：

  10.1021/jm201571p

文献信息

• Contribution of Phosphates and Adenine to the Potency of Adenophostins at the IP₃ Receptor: Synthesis of All Possible Bisphosphates of Adenophostin A
  作者：Kana M. Sureshan、Andrew M. Riley、Mark P. Thomas、Stephen C. Tovey、Colin W. Taylor、Barry V. L. Potter

  DOI：10.1021/jm201571p

  日期：2012.2.23

  Although adenophostin A (AdA), the most potent agonist of D-myoinositol 1,4,5-trisphosphate receptors (IP3R), is thought to mimic IP3, the relative roles of the different phosphate groups and the adenosine motif have not been established. We synthesized all three possible bisphosphate analogues of AdA and glucose 3,4-bisphosphate (7, AdA lacking the 2'-AMP). 2'-Dephospho-AdA (6) was prepared via a novel regioselective dephosphorylation strategy. Assessment of the abilities of these bisphosphates to stimulate intracellular Ca2+ release using recombinant rat type 1 IP3R (IP(3)R1) revealed that 6, a mimic of Ins(4,5)P-2, is only 4-fold less potent than IP3, while 7 is some 400-fold weaker and even 3 ''-dephospho-AdA (5) is measurably active, despite missing one of the vicinal bisphosphate groups normally thought to be crucial for IP3-like activity. Compound 6 is the most potent bisphosphate yet discovered with activity at IP3R. Thus, adenosine has a direct role independent of the 2'-phosphate group in contributing toward the potency of adenophostins, the vicinal bisphosphate motif is not essential for activity at the IP3R, as always thought, and it is possible to design potent agonists with just two of the three phosphates. A model with a possible adenine-R504 interaction supports the activity of 5 and 6 and also allows a reappraisal of the unexpected activity previously reported for the AdA regioisomer 2 ''-phospho-3 ''-dephospho-AdA 40.