[(1S,2R)-2-[(benzoyloxy)methyl]-1-(hydroxymethyl)cyclopropyl]methyl benzoate | 145032-59-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(1S,2R)-2-[(benzoyloxy)methyl]-1-(hydroxymethyl)cyclopropyl]methyl benzoate
• 英文别名: [(1S,2R)-2-benzoyloxymethyl-1-hydroxymethyl]cyclopropylmethyl benzoate；(1S,2R)-{2-[(benzoyloxy)methyl]-1-(hydroxymethyl)cycloprop-1-yl}methyl benzoate；[(1R,2S)-2-(benzoyloxymethyl)-2-(hydroxymethyl)cyclopropyl]methyl benzoate
• CAS: 145032-59-3
• 化学式: C₂₀H₂₀O₅
• 分子量: 340.376
• InChiKey: YRZPQBRVXPDGOX-PXNSSMCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(1S,2R)-2-[(benzoyloxy)methyl]-1-(hydroxymethyl)cyclopropyl]methyl benzoate 在 盐酸 、 4-二甲氨基吡啶 、 18-冠醚-6 、 sodium hydride 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 A-5021
  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：

  ethyl (1S,5R)-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate 在 palladium on activated charcoal 吡啶 、 盐酸 、 sodium tetrahydroborate 、 锂硼氢 、 氢气 、 sodium hydride 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 25.0~72.0 ℃ 、101.33 kPa 条件下， 反应 112.08h， 生成 [(1S,2R)-2-[(benzoyloxy)methyl]-1-(hydroxymethyl)cyclopropyl]methyl benzoate
  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

• Bicyclo[3.1.0]hexanes from sugar-derived diazo compounds and iodonium ylides. Diastereocontrol and synthetic applications
  作者：John K Gallos、Theocharis V Koftis、Zoe S Massen、Constantinos C Dellios、Ioannis T Mourtzinos、Evdoxia Coutouli-Argyropoulou、Alexandros E Koumbis

  DOI：10.1016/s0040-4020(02)01002-5

  日期：2002.9

  The CuI and Rh2(OAc)4 catalyzed decomposition of ethyl 2-diazo-4,5-isopropylidenedioxy-3-oxo-6-heptenoate results in intramolecular cyclopropanation products with opposite diastereoselectivity. In contrast, decomposition of the respective iodonium ylide can proceed without catalysts to give the cyclopropanation products with diastereoselectivity unchangeable by the presence of CuI and Rh2(OAc)4, revealing

  CuI和Rh 2（OAc）4催化2-重氮-4,5-异丙基二烯二氧基-3-氧代-6-庚烯酸乙酯的分解，产生非对映选择性相反的分子内环丙烷化产物。相反，各碘鎓叶立德的分解可在没有催化剂的情况下进行，从而得到具有非对映选择性的环丙烷化产物，由于CuI和Rh 2（OAc）4的存在而不能改变，因此表明，在这种特殊情况下，该反应是亲电子加成碘鎓中心至双键。通过制备许多环戊基，环丙基和双环[3.1.0]己基抗病毒碳环核苷的前体，已经证明了这些反应的综合重要性。
• Carbocyclic nucleoside precursors by intramolecular cyclopropanation of sugar-derived diazo compounds
  作者：John K Gallos、Zoe S Massen、Theocharis V Koftis、Constantinos C Dellios

  DOI：10.1016/s0040-4039(01)01556-8

  日期：2001.10

  Bicyclo[3.1.0]hexane derivatives, selectively prepared by intramolecular cyclopropanation of sugar-derived unsaturated diazo compounds, are common precursors for the sugar moiety of cyclopentane, cyclopropane and bicyclo[3.1.0]hexane nucleosides, such as aristeromycin, the carbocyclic analogue of neplanocin C and the nucleoside A-5021.

  通过分子内糖衍生的不饱和重氮化合物的分子环丙烷化选择性制备的双环[3.1.0]己烷衍生物是环戊烷，环丙烷和双环[3.1.0]己烷核苷的糖部分的常见前体，如阿霉素，碳环类似物奈普洛辛C和核苷A-5021的鉴定。
• Cyclopropane derivative
  申请人：Ajinomoto Co., Inc.

  公开号：EP0502690B1

  公开（公告）日：1999-12-01
• US5342840A
  申请人：——

  公开号：US5342840A

  公开（公告）日：1994-08-30
• US5449840A
  申请人：——

  公开号：US5449840A

  公开（公告）日：1995-09-12