2,2-bis[(tert-butyldimethylsilyloxy)methyl]cyclopropanecarbaldehyde | 144985-59-1

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 2,2-bis[(tert-butyldimethylsilyloxy)methyl]cyclopropanecarbaldehyde
• 英文别名: 2,2-Bis[[tert-butyl(dimethyl)silyl]oxymethyl]cyclopropane-1-carbaldehyde
• CAS: 144985-59-1
• 化学式: C₁₈H₃₈O₃Si₂
• 分子量: 358.669
• InChiKey: YRYBJAQVYALVAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.24
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-bis[(tert-butyldimethylsilyloxy)methyl]cyclopropanecarbaldehyde 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 18-冠醚-6 、 sodium methylate 、 sodium hydride 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.17h， 生成 4-Amino-1-((1S,2S)-1,2-bis-hydroxymethyl-cyclopropylmethyl)-1H-pyrimidin-2-one
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Novel Acyclic Nucleosides:  Discovery of a Cyclopropyl Nucleoside with Potent Inhibitory Activity against Herpesviruses

  摘要：

  A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized stal ting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 mu g/mL against HSV-1 Tomioka vs 0.81 mu g/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.

  DOI：

  10.1021/jm9705869
• 作为产物：
  描述：

  2-乙烯基环丙烷-1,1-二羧酸二乙酯 在 sodium periodate 、 lithium aluminium tetrahydride 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 84.5h， 生成 2,2-bis[(tert-butyldimethylsilyloxy)methyl]cyclopropanecarbaldehyde
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Novel Acyclic Nucleosides:  Discovery of a Cyclopropyl Nucleoside with Potent Inhibitory Activity against Herpesviruses

  摘要：

  A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized stal ting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 mu g/mL against HSV-1 Tomioka vs 0.81 mu g/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.

  DOI：

  10.1021/jm9705869

文献信息

• Using conformationally locked nucleosides to calibrate the anomeric effect: implications for glycosyl bond stability
  作者：Hyung Ryong Moon、Maqbool A. Siddiqui、Guangyu Sun、Igor V. Filippov、Nicholas A. Landsman、Yi-Chien Lee、Kristie M. Adams、Joseph J. Barchi、Jeffrey R. Deschamps、Marc C. Nicklaus、James A. Kelley、Victor E. Marquez

  DOI：10.1016/j.tet.2010.06.044

  日期：2010.8

  and gauche effect play significant roles in steering the North⇆South equilibrium of nucleosides in solution. Two isomeric oxa-bicyclo[3.1.0]hexane nucleosides that are conformationally locked in either the North or the South conformation of the pseudorotational cycle were designed to study the consequences of having the AE operational or not, independent of other parameters. The rigidity of the system

  空间和电子参数，如异头效应 (AE) 和gauche效应在控制溶液中核苷的南北平衡方面起着重要作用。 设计了两个异构的氧杂-双环 [3.1.0] 己烷核苷，它们被构象锁定在假旋转循环的北或南构象中，用于研究 AE 运行与否的后果，独立于其他参数。系统的刚性允许所涉及的轨道的方向设置为“固定”关系，或者是 AE 永久“开启”的反周面，或者是 AE 受损的gauche。这两种替代方案的结果经过高级计算，并通过 X 射线晶体学、糖基键的水解稳定性和 p K a值进行实验测量。
• Cyclopropane derivative
  申请人：Ajinomoto Co., Inc.

  公开号：US05342840A1

  公开（公告）日：1994-08-30

  A cyclopropane derivative of formula (I) ##STR1## wherein B.sup.1 is a purine or pyrimidine residue, R.sup.1 and R.sup.2 are, independently, hydrogen or a protecting group for hydroxyl and each of k, m and n represents, independently, an integer of 1 or 2 is useful for its antiviral effect.

  公式(I)的环丙烷衍生物 ##STR1## 其中B.sup.1是一种嘌呤或嘧啶残基，R.sup.1和R.sup.2分别是氢或羟基的保护基，k、m和n分别表示1或2的整数，该化合物具有抗病毒作用。