1-(2,3-dideoxy-3-fluoro-4,6-O-isopropylidene-β-D-glycerohexopyranosyl)-N(4)-benzoyl cytosine | 1160244-68-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: 1-(2,3-dideoxy-3-fluoro-4,6-O-isopropylidene-β-D-glycerohexopyranosyl)-N(4)-benzoyl cytosine
• 英文别名: N-[1-[(4aR,6R,8R,8aR)-8-fluoro-2,2-dimethyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]-2-oxopyrimidin-4-yl]benzamide
• CAS: 1160244-68-7
• 化学式: C₂₀H₂₂FN₃O₅
• 分子量: 403.41
• InChiKey: GEYINUJRKBDBFY-SRABZTEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  89.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2,3-dideoxy-3-fluoro-4,6-O-isopropylidene-β-D-glycerohexopyranosyl)-N(4)-benzoyl cytosine 在 水 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 以72%的产率得到1-(2,3-dideoxy-3-fluoro-β-D-glycerohexopyranosyl)-N(4)-benzoyl cytosine
  参考文献：
  名称：

  Dideoxy fluoro-ketopyranosyl nucleosides as potent antiviral agents: Synthesis and biological evaluation of 2,3- and 3,4-dideoxy-3-fluoro-4- and -2-keto-β-d-glucopyranosyl derivatives of N4-benzoyl cytosine

  摘要：

  The synthesis of the dideoxy fluoro ketopyramonucleoside analogues, 1-(2,3-dideoxy-3-fluoro-6-O-trityl-beta-D-glycero-hexopyranosyl-4-ulose)-N-4-benzoyl cytosine (7a), 1-(3,4-dideoxy-3-fluoro-6-O-trityl-beta-D-glycero-hexopyranosyl-2-ulose)-N-4-benzoyl cytosine (13a) and their detritylated analogues 8a and 14a, respectively, is described. Condensation of peracetylated 3-deoxy-3-fluoro-D-glucopyranose (1) with silylated N-4-benzoyl cytosine, followed by selective deprotection and isopropylidenation afforded compound 2. Routine deoxygenation at position 2', followed by a deprotection-selective reprotection sequence afforded the partially tritylated dideoxy nucleoside of cytosine 6, which upon oxidation of the free hydroxyl group at the 4'-position, furnished the desired tritylated 2,3-dideoxy-3-fluoro ketonucleoside 7a in equilibrium with its hydrated form 7b. Compound 2 was the starting material for the synthesis of the dideoxy fluoro ketopyranonucleoside 13a. Similarly, several subsequent protection and deprotection steps as well as routine cleoxygenation at position 4', followed by oxidation of the free hydroxyl group at the 2'-position of the partially tritylated dideoxy nucleoside 12, yielded the desired carbonyl compound 13a in equilibrium with its hydrated form 13b. Finally, trityl removal from 7ar/b and 13a/b provided the unprotected 2,3-dideoxy-3-fluoro-4-keto and 3,4-dideoxy-3-fluoro-2-ketopyranonucleoside analogues 8a and 14a, in equilibrium with their gem-diol forms 8b and 14b. None of the compounds showed inhibitory activity against a wide variety of DNA and RNA viruses at subtoxic concentrations, except 7a/b that was highly efficient against rotavirus infection. Nucleoside 7a/b also exhibited cytostatic activity against cells of various cancers. BrdU-cell cycle analysis revealed that the mechanism of cytostatic activity may be related to a delay in G1/S phase and initiation of programmed cell death. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.01.020
• 作为产物：
  描述：

  1-(3-deoxy-3-fluoro-4,6-O-isopropylidene-2-O-phenoxythiocarbonyl-β-D-glucopyranosyl)-N(4)-benzoyl cytosine 在 三正丁基氢锡 、 1,1'-偶氮(氰基环己烷) 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以60%的产率得到1-(2,3-dideoxy-3-fluoro-4,6-O-isopropylidene-β-D-glycerohexopyranosyl)-N(4)-benzoyl cytosine
  参考文献：
  名称：

  Dideoxy fluoro-ketopyranosyl nucleosides as potent antiviral agents: Synthesis and biological evaluation of 2,3- and 3,4-dideoxy-3-fluoro-4- and -2-keto-β-d-glucopyranosyl derivatives of N4-benzoyl cytosine

  摘要：

  The synthesis of the dideoxy fluoro ketopyramonucleoside analogues, 1-(2,3-dideoxy-3-fluoro-6-O-trityl-beta-D-glycero-hexopyranosyl-4-ulose)-N-4-benzoyl cytosine (7a), 1-(3,4-dideoxy-3-fluoro-6-O-trityl-beta-D-glycero-hexopyranosyl-2-ulose)-N-4-benzoyl cytosine (13a) and their detritylated analogues 8a and 14a, respectively, is described. Condensation of peracetylated 3-deoxy-3-fluoro-D-glucopyranose (1) with silylated N-4-benzoyl cytosine, followed by selective deprotection and isopropylidenation afforded compound 2. Routine deoxygenation at position 2', followed by a deprotection-selective reprotection sequence afforded the partially tritylated dideoxy nucleoside of cytosine 6, which upon oxidation of the free hydroxyl group at the 4'-position, furnished the desired tritylated 2,3-dideoxy-3-fluoro ketonucleoside 7a in equilibrium with its hydrated form 7b. Compound 2 was the starting material for the synthesis of the dideoxy fluoro ketopyranonucleoside 13a. Similarly, several subsequent protection and deprotection steps as well as routine cleoxygenation at position 4', followed by oxidation of the free hydroxyl group at the 2'-position of the partially tritylated dideoxy nucleoside 12, yielded the desired carbonyl compound 13a in equilibrium with its hydrated form 13b. Finally, trityl removal from 7ar/b and 13a/b provided the unprotected 2,3-dideoxy-3-fluoro-4-keto and 3,4-dideoxy-3-fluoro-2-ketopyranonucleoside analogues 8a and 14a, in equilibrium with their gem-diol forms 8b and 14b. None of the compounds showed inhibitory activity against a wide variety of DNA and RNA viruses at subtoxic concentrations, except 7a/b that was highly efficient against rotavirus infection. Nucleoside 7a/b also exhibited cytostatic activity against cells of various cancers. BrdU-cell cycle analysis revealed that the mechanism of cytostatic activity may be related to a delay in G1/S phase and initiation of programmed cell death. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.01.020

文献信息

• Dideoxy fluoro-ketopyranosyl nucleosides as potent antiviral agents: Synthesis and biological evaluation of 2,3- and 3,4-dideoxy-3-fluoro-4- and -2-keto-β-d-glucopyranosyl derivatives of N4-benzoyl cytosine
  作者：Stella Manta、Evangelia Tsoukala、Niki Tzioumaki、Aleš Goropevšek、Ravi Teja Pamulapati、Avrelija Cencič、Jan Balzarini、Dimitri Komiotis

  DOI：10.1016/j.ejmech.2009.01.020

  日期：2009.6

  The synthesis of the dideoxy fluoro ketopyramonucleoside analogues, 1-(2,3-dideoxy-3-fluoro-6-O-trityl-beta-D-glycero-hexopyranosyl-4-ulose)-N-4-benzoyl cytosine (7a), 1-(3,4-dideoxy-3-fluoro-6-O-trityl-beta-D-glycero-hexopyranosyl-2-ulose)-N-4-benzoyl cytosine (13a) and their detritylated analogues 8a and 14a, respectively, is described. Condensation of peracetylated 3-deoxy-3-fluoro-D-glucopyranose (1) with silylated N-4-benzoyl cytosine, followed by selective deprotection and isopropylidenation afforded compound 2. Routine deoxygenation at position 2', followed by a deprotection-selective reprotection sequence afforded the partially tritylated dideoxy nucleoside of cytosine 6, which upon oxidation of the free hydroxyl group at the 4'-position, furnished the desired tritylated 2,3-dideoxy-3-fluoro ketonucleoside 7a in equilibrium with its hydrated form 7b. Compound 2 was the starting material for the synthesis of the dideoxy fluoro ketopyranonucleoside 13a. Similarly, several subsequent protection and deprotection steps as well as routine cleoxygenation at position 4', followed by oxidation of the free hydroxyl group at the 2'-position of the partially tritylated dideoxy nucleoside 12, yielded the desired carbonyl compound 13a in equilibrium with its hydrated form 13b. Finally, trityl removal from 7ar/b and 13a/b provided the unprotected 2,3-dideoxy-3-fluoro-4-keto and 3,4-dideoxy-3-fluoro-2-ketopyranonucleoside analogues 8a and 14a, in equilibrium with their gem-diol forms 8b and 14b. None of the compounds showed inhibitory activity against a wide variety of DNA and RNA viruses at subtoxic concentrations, except 7a/b that was highly efficient against rotavirus infection. Nucleoside 7a/b also exhibited cytostatic activity against cells of various cancers. BrdU-cell cycle analysis revealed that the mechanism of cytostatic activity may be related to a delay in G1/S phase and initiation of programmed cell death. (C) 2009 Elsevier Masson SAS. All rights reserved.