1-(3,5-di-O-benzoyl-β-D-xylofuranosyl)uracil | 99152-41-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(3,5-di-O-benzoyl-β-D-xylofuranosyl)uracil
• 英文别名: [(2R,3R,4R,5R)-3-benzoyloxy-5-(2,4-dioxopyrimidin-1-yl)-4-hydroxyoxolan-2-yl]methyl benzoate
• CAS: 99152-41-7
• 化学式: C₂₃H₂₀N₂O₈
• 分子量: 452.42
• InChiKey: JARFLQGNRAJUDJ-RSPOEFSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(3,5-di-O-benzoyl-β-D-xylofuranosyl)uracil 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Highly β-stereoselective nucleosidation from α-d-xylo- and α-d-ribo-furanose 1,2-thiocarbonates

  摘要：

  Cyclic 1,2-thiocarbonates of alpha-D-xylo- and alpha-D-ribo-furanoses were found to be excellent glycosyl donors in mild NIS-mediated nucleophilic substitution reactions, affording beta-nucleosides with complete stereo selectivity and moderate to high yields after treatment with persilylated pyrimidinic bases. The nucleophile is believed to open the thiocarbonate ring at the anomeric position presumably via an S(N)2 mechanism. Participation of the nucleobase silylating agent [N,O-bis(trimethylsilyl)acetamide] in the mechanism of the nucleosidation step was shown, where a large excess of it has been proven to be necessary in order to achieve high yields. Absolute configurations at C-1' were ascertained by chemical correlation synthesizing the corresponding 2,2'-anhydronucleosides. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.12.037
• 作为产物：
  描述：

  1-(2'-O-acetamidomercaptocarbonyl-3',5'-di-O-benzoyl-β-D-xylo-furanosyl)uracil 在 三乙烯二胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以85%的产率得到1-(3,5-di-O-benzoyl-β-D-xylofuranosyl)uracil
  参考文献：
  名称：

  Highly β-stereoselective nucleosidation from α-d-xylo- and α-d-ribo-furanose 1,2-thiocarbonates

  摘要：

  Cyclic 1,2-thiocarbonates of alpha-D-xylo- and alpha-D-ribo-furanoses were found to be excellent glycosyl donors in mild NIS-mediated nucleophilic substitution reactions, affording beta-nucleosides with complete stereo selectivity and moderate to high yields after treatment with persilylated pyrimidinic bases. The nucleophile is believed to open the thiocarbonate ring at the anomeric position presumably via an S(N)2 mechanism. Participation of the nucleobase silylating agent [N,O-bis(trimethylsilyl)acetamide] in the mechanism of the nucleosidation step was shown, where a large excess of it has been proven to be necessary in order to achieve high yields. Absolute configurations at C-1' were ascertained by chemical correlation synthesizing the corresponding 2,2'-anhydronucleosides. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.12.037

文献信息

• Methods of treating hepatitis delta virus infection with beta-l-2'-deoxy-nucleosides
  申请人：——

  公开号：US20020035085A1

  公开（公告）日：2002-03-21

  A method and composition for treating a host infected with hepatitis D comprising administering an effective hepatitis D treatment amount of a described 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof.

  一种治疗感染乙型肝炎的宿主的方法和组合物，包括给予所述2'-脱氧-β-L-赤霉糖核苷或其药用可接受的盐或前药的有效乙型肝炎治疗剂量。
• Synthèse de nucléosides pyrimidiques non protégés en O-2′ à partir de sulfites cycliques en C-1—C-2
  作者：Christian H. Gagnieu、Alain Guiller、Henri Pacheco

  DOI：10.1016/0008-6215(88)80080-6

  日期：1988.9

  was readily hydrolyzed in slightly acid conditions to give in almost quantitative yield 1-(3,5,6-tri- O -benzoyl-β- d -glucofuranosyl)uracil. This new synthetic method for nucleosides unprotected at O-2′ was also tested in other sugar series. In some cases, only the 1′,2′- trans -nucleosides were obtained, but in others, small yields (3–10%) of 1′,2′- cis -nucleosides were detected. The α-to-β ratio

  摘要在没有任何催化剂的熔融过程中，用过量的双（三甲基硅）尿嘧啶处理3,5,6-三-O-苯甲酰基-α-d-葡萄糖呋喃糖1,2-亚硫酸盐，得到了1-（-）极好的收率。 3,5,6-三-O-苯甲酰基-2-O-三甲基甲硅烷基-β-d-葡萄糖基呋喃糖基）尿嘧啶，在弱酸性条件下容易水解，几乎可以定量得到1-（3,5,6-tri -O-苯甲酰基-β-d-葡糖呋喃糖基）尿嘧啶。在其他糖系列中也测试了这种在O-2'处未保护的核苷的新合成方法。在某些情况下，仅获得了1'，2'-顺式核苷，而在其他情况下，仅检测到了1'，2'-顺式核苷的少量收率（3-10％）。α与β之比似乎取决于反应温度。2,4-二甲氧基嘧啶还与糖1,2-亚硫酸盐和4-O-甲基-1-（3,5，
• 2' or 3' -deoxy and 2' , 3' -dideoxy-beta-L-pentofuranonucleo-side compounds, method of preparation and application in therapy, especially as anti-viral agents
  申请人：Gosselin Gilles

  公开号：US20050101776A1

  公开（公告）日：2005-05-12

  Method for the sterospecific preparation of 2′ or 3′ deoxy and 2′,3′-dideoxy-β-L-pentafuranonucleoside compounds. 2′ or 3′ deoxy and 2′,3′-dideoxy-β-L-pentofuranonucleoside compounds are also described. Finally, the invention concerns the use of these compounds, and particularly 2′,3′dideoxy-β-L-fluorocytidine, as drugs, and especially as anti-viral agents.

  一种立体选择性制备2′或3′去氧和2′,3′-二去氧-β-L-戊糖核苷化合物的方法。还描述了2′或3′去氧和2′,3′-二去氧-β-L-戊糖核苷化合物。最后，本发明涉及这些化合物的用途，特别是2′,3′-二去氧-β-L-氟胞嘧啶作为药物，特别是作为抗病毒剂。
• 2' or 3' -deoxy and 2', 3' -dideoxy-beta-L-pentofuranonucleo-side compounds, method of preparation and application in therapy, especially as anti- viral agents
  申请人：——

  公开号：US20020120130A1

  公开（公告）日：2002-08-29

  Method for the sterospecific preparation of 2′ or 3′ deoxy and 2′, 3′-dideoxy-&bgr;-L-pentofuranonucleoside compounds. 2′ or 3′ deoxy and 2′, 3′-dideoxy-&bgr;-L-pentofuranonucleoside compounds are also described. Finally, the invention concerns the use of these compounds, and particularly 2′, 3′ dideoxy-&bgr;-L-fluorocytidine, as drugs, and especially as anti-viral agents.

  这是一种用于立体选择性制备2'或3'脱氧和2'，3'-二脱氧-β-L-戊糖呋喃核苷化合物的方法。本发明还描述了2'或3'脱氧和2'，3'-二脱氧-β-L-戊糖呋喃核苷化合物。最后，本发明涉及这些化合物的用途，特别是2'，3'二脱氧-β-L-氟胞嘧啶作为药物，特别是作为抗病毒药物。
• Beta-L-2'-deoxynucleosides for the treatment of resistant HBV strains and combination therapies
  申请人：Standring David

  公开号：US20050080034A1

  公开（公告）日：2005-04-14

  It has been discovered that β-L-2′-deoxynucleosides are active against drug-resistant hepatitis B virus with mutations. A method for treating lamivudine resistant HBV (M552V) in a host is provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug. In addition, a method for preventing lamivudine resistant HBV (M552V) mutation from occurring in a naïve host is provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug. A method for preventing and/or suppressing the emergence of the HBV double mutant (L528M/M552V) in a host is also provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug.

  已经发现β-L-2'-脱氧核苷可以对具有突变的耐药性乙型肝炎病毒产生活性。提供了一种治疗宿主中拉米夫定耐药性HBV（M552V）的方法，包括给予β-L-2'-脱氧核苷或其药学上可接受的盐、酯或前药。此外，提供了一种防止拉米夫定耐药性HBV（M552V）突变在未接触过的宿主中发生的方法，包括给予β-L-2'-脱氧核苷或其药学上可接受的盐、酯或前药。还提供了一种防止和/或抑制宿主中HBV双突变体（L528M / M552V）出现的方法，包括给予β-L-2'-脱氧核苷或其药学上可接受的盐、酯或前药。