(3aR,4R,6aR)-(6-benzyloxymethyl-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yloxy)-tert-butyl-diphenyl-silane | 491577-97-0

• 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: (3aR,4R,6aR)-(6-benzyloxymethyl-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yloxy)-tert-butyl-diphenyl-silane
• 英文别名: [(3aR,6R,6aR)-5-fluoro-2,2-dimethyl-4-(phenylmethoxymethyl)-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]oxy-tert-butyl-diphenylsilane
• CAS: 491577-97-0
• 化学式: C₃₂H₃₇FO₄Si
• 分子量: 532.727
• InChiKey: BYGLQNROXOWSRF-DYIKCSJPSA-N

物化性质

• 沸点：
  557.3±50.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.91
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3aR,4R,6aR)-(6-benzyloxymethyl-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yloxy)-tert-butyl-diphenyl-silane 在 18-冠醚-6 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3aS,4S,6aR)-9-(6-benzyloxymethyl-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yl)-9H-purin-6-ylamine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Halo-neplanocin A as Novel Mechanism-Based Inhibitors ofS-Adenosylhomocysteine Hydrolase

  摘要：

  Halogenated analogues of neplanocin A were synthesized from the key intermediate 1, among which fluoro-neplanocin A was found to be novel mechanism-based irreversible inhibitor of S-Adenosylhomocysteine hydrolase.

  DOI：

  10.1081/ncn-120021961
• 作为产物：
  描述：

  (4R,5R)-3-benzyloxymethyl-4,5-isopropylidenedioxycyclopent-2-enone 在 吡啶 、 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 cerium(III) chloride 、 碘 、 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (3aR,4R,6aR)-(6-benzyloxymethyl-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yloxy)-tert-butyl-diphenyl-silane
  参考文献：
  名称：

  设计，合成和生物学评估氟内啡肽A作为新型的基于机制的S-腺苷同型半胱氨酸水解酶抑制剂。

  摘要：

  Fluoroneplanocin A（12）被设计为一种新型的基于机制的S-腺苷同型半胱氨酸水解酶（SAH）抑制剂，并通过亲电乙烯基氟化反应（-78℃下的n-BuLi，N-氟苯磺酰亚胺）有效合成。氟尿素链球菌素A的SAH抑制活性比亲本Neplanocin A强2倍。这项工作中发现的不可逆抑制的新机制可能为设计通过SAH抑制作用的另一类抗病毒药提供新的选择。

  DOI：

  10.1021/jm025557z

文献信息

• 6′-Fluoro-3-deazaneplanocin: Synthesis and antiviral properties, including Ebola
  作者：Chong Liu、Qi Chen、Steven Cardinale、Terry L. Bowlin、Stewart W. Schneller

  DOI：10.1016/j.bmcl.2018.10.030

  日期：2018.12

  convenient stereospecific synthesis of 6′-fluoro-3-deazaneplanocin (6) has been accomplished from d-ribose in 15 steps. It is reported to possess significant activity towards Ebola (Zaire, Vero, μM: EC50 < 0.36; CC50 125; SI > 347) with moderate inhibition of the target enzyme (S-adenosylhomocysteine hydrolase), which did not correlate directly with its anti-Ebola effects. Compound 6, with limited cytotoxicity

  从15个步骤中，由d-核糖即可完成6'-氟-3-脱氮烷普莱辛霉素（6）的便捷立体定向合成。据报道它对埃博拉病毒具有显着活性（Zaire，Vero，μM：EC 50  <0.36; CC 50 125; SI> 347），对目标酶（S-腺苷同型半胱氨酸水解酶）具有中等抑制作用，而该酶与其酶活性没有直接相关性抗埃博拉病毒的作用。具有有限细胞毒性的化合物6也显示出对麻疹，H1N1和Pichinde的活性。
• Fluorocyclopentenyl-cytosine with Broad Spectrum and Potent Antitumor Activity
  作者：Won Jun Choi、Hwa-Jin Chung、Girish Chandra、Varughese Alexander、Long Xuan Zhao、Hyuk Woo Lee、Akshata Nayak、Mahesh S. Majik、Hea Ok Kim、Jin-Hee Kim、Young B. Lee、Chang H. Ahn、Sang Kook Lee、Lak Shin Jeong

  DOI：10.1021/jm3004009

  日期：2012.5.10

  On the basis of the potent biological activity of cyclopentenyl-pyrimidines, fluorocyclopentenyl-pyrimidines were designed and synthesized from D-ribose. Among these, the cytosine derivative 5a showed highly potent antigrowth effects in a broad range of tumor cell lines and very potent antitumor activity in a nude mouse tumor xenograft model implanted with A549 human lung cancer cells. However, its 2'-deoxycytidine derivative 5b did not show any antigrowth effects, indicating that 2'-hydroxyl group is essential for the biological activity.
• X-ray Crystal Structure and Binding Mode Analysis of Human <i>S</i>-Adenosylhomocysteine Hydrolase Complexed with Novel Mechanism-Based Inhibitors, Haloneplanocin A Analogues
  作者：Kang Man Lee、Won Jun Choi、Yoonji Lee、Hyun Joo Lee、Long Xuan Zhao、Hyuk Woo Lee、Jae Gyu Park、Hea Ok Kim、Kwang Yeon Hwang、Yong-Seok Heo、Sun Choi、Lak Shin Jeong

  DOI：10.1021/jm1010836

  日期：2011.2.24

  The X-ray crystal structure of human S-adenosylhomocysteine (AdoHcy) hydrolase was first determined as a tetrameric form bound with the novel mechanism-based inhibitor fluoroneplanocin A (4b). The crystallized enzyme complex showed the closed conformation and turned out to be the intermediate of mechanism-based inhibition. It confirmed that the cofactor depletion by 3'-oxidation of fluoroneplanocin A contributes to the enzyme inhibition along with the irreversible covalent modification of AdoHcy hydrolase. In addition, a series of haloneplanocin A analogues (4b-e and 5b-e) were designed and synthesized to characterize the binding role and reactivity of the halogen substituents and the 4'-CH2OH group. The biological evaluation and molecular modeling studies identified the key pharmacophores and structural requirements for the inhibitor binding of AdoHcy hydrolase. The inhibitory activity was decreased as the size of the halogen atom increased and/or if the 4'-CH2OH group was absent. These results could be utilized to design new therapeutic agents operating via AdoHcy hydrolase inhibition.
• Synthesis and Antitumor Activity of Fluorocyclopentenyl-Pyrimidines
  作者：Lak Shin Jeong、Long Xuan Zhao、Won Jun Choi、Shantanu Pal、Yeon Hee Park、Sang Kook Lee、Moon Woo Chun、Young B. Lee、Chang Ho Ahn、Hyung Ryong Moon

  DOI：10.1080/15257770701490852

  日期：2007.11.26

  Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6-9 was enantiopurely accomplished employing oxidative rearrangement, RCM reaction and electrophilic fluorination starting from D-ribose. Cytosine analog 8 was found to exhibit significant anticancer activity in various human tumor cell lines.
• J. Med. Chem. 2012, 55, 4521-4525
  作者：

  DOI：——

  日期：——