(3aS,4R,6aR)-6-[((苄氧基)甲基]-5-氟-2,2-二甲基-2H,3aH,4H,6aH-环戊基[d][1,3]二恶酚-4-醇 | 491578-02-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (3aS,4R,6aR)-6-[((苄氧基)甲基]-5-氟-2,2-二甲基-2H,3aH,4H,6aH-环戊基[d][1,3]二恶酚-4-醇
• 英文名称: (3aS,4R,6aR)-6-benzyloxymethyl-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-ol
• 英文别名: (3aS,4R,6aR)-6-(benzyloxymethyl)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol；6-benzyloxymethyl-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-ol；(1R,4R,5S)-3-(benzyloxymethyl)-2(3)-en-2-fluoro-4,5-(O-isopropylidenedioxy)cyclo-pentan-1-ol；(3aS,4R,6aR)-6-[(benzyloxy)methyl]-5-fluoro-2,2-dimethyl-2H,3aH,4H,6aH-cyclopenta[d][1,3]dioxol-4-ol；(3aR,6R,6aS)-5-fluoro-2,2-dimethyl-4-(phenylmethoxymethyl)-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-6-ol
• CAS: 491578-02-0
• 化学式: C₁₆H₁₉FO₄
• 分子量: 294.323
• InChiKey: IIASTRMJADMUFQ-ZNMIVQPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3aS,4R,6aR)-6-[((苄氧基)甲基]-5-氟-2,2-二甲基-2H,3aH,4H,6aH-环戊基[d][1,3]二恶酚-4-醇 在 吡啶 、 偶氮二甲酸二异丙酯 、 氨 、 三溴化硼 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 16.75h， 生成 O-((8S,9S,9aR)-8-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-7-fluoro-2,2,4,4-tetraisopropyl-6,8,9,9a-tetrahydrocyclopenta[f][1,3,5,2,4]trioxadisilocin-9-yl) O-phenyl carbonothioate
  参考文献：
  名称：

  Fluorocyclopentenyl-cytosine with Broad Spectrum and Potent Antitumor Activity

  摘要：

  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.

  DOI：

  10.1021/jm3004009
• 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 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 (3aS,4R,6aR)-6-[((苄氧基)甲基]-5-氟-2,2-二甲基-2H,3aH,4H,6aH-环戊基[d][1,3]二恶酚-4-醇
  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

• Regio- and stereoselective synthesis of 2′-β-substituted-fluoroneplanocin A analogues as potential anticancer agents
  作者：Akshata Nayak、Pramod K. Sahu、Jayoung Song、Sang Kook Lee、Lak Shin Jeong

  DOI：10.1039/c5ob01348h

  日期：——

  A series of 2′-β-substituted-6′-fluoro-cyclopentenyl-pyrimidines and -purines 8 and 9 were successfully synthesized from D-ribose in a regio- and stereoselective manner. The functionalization at the C2-position of 6′-fluoro-cyclopentenyl nucleosides was achieved via regioselective protection of a hydroxyl group at the C3-position and stereoselective formation of C2-triflate followed by direct SN2 reaction

  从D-核糖以区域和立体选择性的方式成功地合成了一系列的2'-β-取代-6'-氟-环戊烯基-嘧啶和-嘌呤8和9。6'-氟-环戊烯基核苷在C2位置的官能化是通过在C3位置对羟基进行区域选择性保护和立体选择性形成C2-三氟甲磺酸酯，然后与氟或叠氮亲核试剂进行直接S N 2反应来实现的。对所有合成的化合物在几种肿瘤细胞系中的抗癌活性进行了评估，但发现它们既没有活性也没有毒性。
• 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。
• 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.
• Synthesis and Biological Evaluation of Halo-neplanocin A as Novel Mechanism-Based Inhibitors of<i>S</i>-Adenosylhomocysteine Hydrolase
  作者：Lak Shin Jeong、Hyung Ryong Moon、Jae Gyu Park、Dae Hong Shin、Won Jun Choi、Kang Man Lee、Hea Ok Kim、Moon Woo Chun、Hee-Doo Kim、Joong Hyup Kim

  DOI：10.1081/ncn-120021961

  日期：2003.10

  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.