(+)-(2R,4R)-4-(azidomethyl)-2-tert-butyl-1,3-dioxane | 872104-78-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (+)-(2R,4R)-4-(azidomethyl)-2-tert-butyl-1,3-dioxane
• 英文别名: (2R,4R)-4-(azidomethyl)-2-tert-butyl-1,3-dioxane
• CAS: 872104-78-4
• 化学式: C₉H₁₇N₃O₂
• 分子量: 199.253
• InChiKey: HGNSOMBLTHLCBD-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-(2R,4R)-4-(azidomethyl)-2-tert-butyl-1,3-dioxane 在 Amberlyst 15 acidic form 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以92%的产率得到(-)-(R)-4-azidobutane-1,3-diol
  参考文献：
  名称：

  Structure–affinity relationship studies of non-competitive NMDA receptor antagonists derived from dexoxadrol and etoxadrol

  摘要：

  The synthesis and NMDA receptor affinity of ring and side-chain homologues of etoxadrol and dexoxadrol are described. For the regioselective synthesis of etoxadrol homologues, the regioisomeric 4-azidobutanediols (+/-)-9 and (+/-)-14 were employed. A synthesis of the enantiomerically pure azidobutanediols (S)-, (R)-9 and (S)-, (R)-14 was developed and the homochiral building blocks were used for the synthesis of enantiomerically pure etoxadrol and dexoxadrol homologues. The affinity of the racemic and enantiomerically pure primary amines toward the phencyclidine binding site of the NMDA receptor was investigated in receptor binding studies with tritium labeled [H-3]-(+)-MK-801 as radioligand. Benzaldehyde derivatives (+/-)-12a, (+/-)-13a, and (+/-)-16a bearing a proton at the acetalic position do not interact significantly with the NMDA receptor. An enantioselective NMDA receptor binding was observed for the trans-configured 2-(2-ethyl-2-phenyl-1,3-dioxolan-4-yl)ethanamine 13b, the (2-ethyl-2-phenyl-1,3-dioxan-4-yl)methanamine 16b, and the (2,2-diphenyl-1,3-dioxan-4-yl)methanamine 16c. The NMDA receptor affinity of these compounds resides almost exclusively in the (S)-configured enantiomers (2S,4S)-13b, (2S,4S)-16b, and (4S)-16c. The lowest K-i-value in this series was found for the (2S,4S)-configured 1,3-dioxolane (2S,4S)-13b (K-i = 69 nM), which is in the range of the Ki-value of the lead compounds etoxadrol and dexoxadrol, indicating that the 2-aminoethyl and the piperidin-2-yl substituents lead to similar NMDA receptor interactions. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.030
• 作为产物：
  描述：

  (-)-[(2R,4R)-(2-tert-butyl-1,3-dioxan-4-yl)methyl]tosylate 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以67%的产率得到(+)-(2R,4R)-4-(azidomethyl)-2-tert-butyl-1,3-dioxane
  参考文献：
  名称：

  Structure–affinity relationship studies of non-competitive NMDA receptor antagonists derived from dexoxadrol and etoxadrol

  摘要：

  The synthesis and NMDA receptor affinity of ring and side-chain homologues of etoxadrol and dexoxadrol are described. For the regioselective synthesis of etoxadrol homologues, the regioisomeric 4-azidobutanediols (+/-)-9 and (+/-)-14 were employed. A synthesis of the enantiomerically pure azidobutanediols (S)-, (R)-9 and (S)-, (R)-14 was developed and the homochiral building blocks were used for the synthesis of enantiomerically pure etoxadrol and dexoxadrol homologues. The affinity of the racemic and enantiomerically pure primary amines toward the phencyclidine binding site of the NMDA receptor was investigated in receptor binding studies with tritium labeled [H-3]-(+)-MK-801 as radioligand. Benzaldehyde derivatives (+/-)-12a, (+/-)-13a, and (+/-)-16a bearing a proton at the acetalic position do not interact significantly with the NMDA receptor. An enantioselective NMDA receptor binding was observed for the trans-configured 2-(2-ethyl-2-phenyl-1,3-dioxolan-4-yl)ethanamine 13b, the (2-ethyl-2-phenyl-1,3-dioxan-4-yl)methanamine 16b, and the (2,2-diphenyl-1,3-dioxan-4-yl)methanamine 16c. The NMDA receptor affinity of these compounds resides almost exclusively in the (S)-configured enantiomers (2S,4S)-13b, (2S,4S)-16b, and (4S)-16c. The lowest K-i-value in this series was found for the (2S,4S)-configured 1,3-dioxolane (2S,4S)-13b (K-i = 69 nM), which is in the range of the Ki-value of the lead compounds etoxadrol and dexoxadrol, indicating that the 2-aminoethyl and the piperidin-2-yl substituents lead to similar NMDA receptor interactions. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.030

文献信息

• Synthesis of Regioisomeric Azidobutanediols
  作者：Bernhard Wünsch、Marion Aepkers

  DOI：10.1055/s-2004-822329

  日期：——

  Investigations to control the regioselectivity during the acetalization of pivalaldehyde (7) with butane-1,2,4-triol (4) were performed. Thermodynamic control led to the regioisomeric acetals 8 and 9 in the ratio 76:24, whereas kinetic control favored the five-membered acetal 9 (8/9 30:70). Tosylation, nucleophilic substitution with NaN3, and subsequent methanolysis of the regioisomeric acetals 8 and 9 provided the regioisomeric 4-azidobutanediols 5 and 6, which are considered as valuable building blocks for the synthesis of novel NMDA-receptor antagonists.

  研究人员对新戊醛（7）与丁烷-1,2,4-三醇（4）乙缩醛化过程中的区域选择性进行了控制。在热力学控制下，生成了比例为 76:24 的异构乙缩醛 8 和 9，而在动力学控制下，则生成了五元乙缩醛 9（8/9 30:70）。通过对甲苯磺酸化、NaN3 亲核取代以及随后的甲醇分解，得到了 4-叠氮丁二醇 5 和 6，它们被认为是合成新型 NMDA 受体拮抗剂的重要组成单元。