1,2-anhydro-2-C-methyl-3,5-di-O-(4-methylbenzoyl)-α-D-ribofuranose | 741686-50-0

• 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: 1,2-anhydro-2-C-methyl-3,5-di-O-(4-methylbenzoyl)-α-D-ribofuranose
• 英文别名: 1,2-anhydro-3,5-di-O-(4-methylbenzoyl)-2-C-methyl-β-D-ribofuranose；1,2-anhydro-3,5-di-O-(p-toluoyl)-2-C-methyl-α-D-ribofuranose；1,2-Anhydro-3,5-di-O-(p-toluoyl)-2-C-methyl-alpha-D-ribofuranose；[(1R,3R,4R,5R)-5-methyl-4-(4-methylbenzoyl)oxy-2,6-dioxabicyclo[3.1.0]hexan-3-yl]methyl 4-methylbenzoate
• CAS: 741686-50-0
• 化学式: C₂₂H₂₂O₆
• 分子量: 382.413
• InChiKey: ZOJWBRDFEZHNTI-MCEIDBOGSA-N

物化性质

• 沸点：
  504.6±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  74.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,2-anhydro-2-C-methyl-3,5-di-O-(4-methylbenzoyl)-α-D-ribofuranose 在 N,N-二甲基乙酰胺 、 sodium hydride 、 正丁胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 9.0h， 生成 7-(2-C-甲基-beta-D-呋喃核糖基)-7H-吡咯并[2,3-d]嘧啶-4-胺
  参考文献：
  名称：

  Practical Synthesis of a Potent Hepatitis C Virus RNA Replication Inhibitor

  摘要：

  A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described. Starting with the inexpensive diacetone glucose, the 12-step synthesis features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate. This is followed by a highly selective glycosidation to couple the C-2 branched furanose epoxide with deazapurine.

  DOI：

  10.1021/jo0491096
• 作为产物：
  描述：

  2-C-methyl-3,5-di-O-(4-methylbenzoyl)-D-ribofuranose 在 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.33h， 生成 1,2-anhydro-2-C-methyl-3,5-di-O-(4-methylbenzoyl)-α-D-ribofuranose
  参考文献：
  名称：

  Sugar-modified derivatives of cytostatic 6-(het)aryl-7-deazapurine nucleosides: 2′-C-methylribonucleosides, arabinonucleosides and 2′-deoxy-2′-fluoroarabinonucleosides

  摘要：

  一系列新型糖基修饰的细胞毒性6-杂环-7-脱氮嘌呤核苷衍生物：2'-C-甲基核糖核苷、阿拉伯核苷和带有烷基、芳基和杂芳基团的位置6的2'-脱氧-2'-氟阿拉伯核苷，通过钯催化的相应（受保护的）6-氯（7-氟）-7-脱氮嘌呤核苷与（杂）芳基硼、杂芳基锡烷和三甲基铝的交叉偶联反应制备，最终通过去保护反应得到。关键中间体6-氯-7-脱氮嘌呤2'-C-甲基-β-D-核糖呋喃苷通过具有立体选择性的核碱基负离子糖基化与对甲苯基保护的1,2-脱氧-2'-C-甲基核糖呋喃糖制备而成。1,2-脱氧糖在3步合成，起始原料为易得的2-C-甲基核糖内酯。6-氯-7-脱氮嘌呤阿拉伯呋喃苷中间体通过从3′,5′-保护的6-氯-7-脱氮嘌呤核糖苷经2'-羟基氧化再还原而获得。所有制备的化合物均未显示出明显的细胞毒性或抗病毒活性。

  DOI：

  10.1135/cccc2011082

文献信息

• Process for preparing branched ribonucleosides from 1,2-anhydroribofuranose intermediates
  申请人：Xu Feng

  公开号：US20070037771A1

  公开（公告）日：2007-02-15

  A process is provided for the preparation of branched-chain ribonucleosides of formula (I) from the 1,2-anhydro derivatives of formula (II). The compounds of formula (I) are inhibitors of HCV polymerase useful in the treatment of HCV infection.

  提供一种从公式（II）的1,2-去水衍生物制备支链核糖核苷（I）的方法。公式（I）的化合物是HCV聚合酶的抑制剂，用于治疗HCV感染。
• Fluorinated Pyrrolo[2,3-D]Pyrimidine Nucleosides for the Treatment of Rna-Dependent Rna Viral Infection
  申请人：MacCoss Malcolm

  公开号：US20080280842A1

  公开（公告）日：2008-11-13

  The present invention provides fluorinated pyrrolo[2,3,d]pyrimidine nucleoside compounds which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such fluorinated pyrrolo[2,3-d]pyrimidine nucleoside alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the fluorinated pyrrolo[2,3-d]pyrimidine nucleoside of the present invention.

  本发明提供了一种氟代吡咯并[2,3,d]嘧啶核苷化合物，其是RNA依赖性RNA病毒聚合酶的抑制剂。这些化合物是RNA依赖性RNA病毒复制的抑制剂，可用于治疗RNA依赖性RNA病毒感染。它们特别适用于作为丙型肝炎病毒（HCV）NS5B聚合酶抑制剂的前体，作为HCV复制抑制剂的前体，和/或用于治疗丙型肝炎感染。该发明还描述了含有这种氟代吡咯并[2,3-d]嘧啶核苷单独或与其他对RNA依赖性RNA病毒感染，特别是HCV感染活性的药物组合物。还公开了使用本发明的氟代吡咯并[2,3-d]嘧啶核苷抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。
• WO2006/65335
  申请人：——

  公开号：——

  公开（公告）日：——
• Practical Synthesis of a Potent Hepatitis C Virus RNA Replication Inhibitor
  作者：Matthew M. Bio、Feng Xu、Marjorie Waters、J. Michael Williams、Kimberly A. Savary、Cameron J. Cowden、Chunhua Yang、Elizabeth Buck、Zhiguo J. Song、David M. Tschaen、R. P. Volante、Robert A. Reamer、Edward J. J. Grabowski

  DOI：10.1021/jo0491096

  日期：2004.9.1

  A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described. Starting with the inexpensive diacetone glucose, the 12-step synthesis features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate. This is followed by a highly selective glycosidation to couple the C-2 branched furanose epoxide with deazapurine.
• Sugar-modified derivatives of cytostatic 6-(het)aryl-7-deazapurine nucleosides: 2′-C-methylribonucleosides, arabinonucleosides and 2′-deoxy-2′-fluoroarabinonucleosides
  作者：Petr Nauš、Pavla Perlíková、Radek Pohl、Michal Hocek

  DOI：10.1135/cccc2011082

  日期：——

  A series of novel sugar-modified derivatives of cytostatic 6-hetaryl-7-deazapurine ribonucleosides: 2′-C-methylribonucleosides, arabinonucleosides and 2′-deoxy-2′-fluoroarabinonucleosides bearing an alkyl, aryl and hetaryl group in position 6 were prepared by palladium catalyzed cross-coupling reactions of corresponding (protected) 6-chloro-(7-fluoro)-7-deazapurine nucleosides with (het)arylboronic, hetarylstannanes and trimethylaluminium eventually followed by deprotection. Key intermediate 6-chloro-7-deazapurine 2′-C-methyl-β-D-ribofuranoside was prepared via a stereoselective nucleobase anion glycosylation with toluoyl-protected 1,2-anhydro-2-C-methylribofuranose. The 1,2-anhydro sugar was synthesized in 3 steps starting from readily available 2-C-methylribonolactone. The 6-chloro-7-deazapurine arabinofuranoside intermediate was obtained by epimerization from 3′,5′-protected 6-chloro-7-deazapurine ribofuranoside via 2′-hydroxyl oxidation followed by reduction. None of the prepared compounds showed any considerable cytostatic or antiviral activity.

  一系列新型糖基修饰的细胞毒性6-杂环-7-脱氮嘌呤核苷衍生物：2'-C-甲基核糖核苷、阿拉伯核苷和带有烷基、芳基和杂芳基团的位置6的2'-脱氧-2'-氟阿拉伯核苷，通过钯催化的相应（受保护的）6-氯（7-氟）-7-脱氮嘌呤核苷与（杂）芳基硼、杂芳基锡烷和三甲基铝的交叉偶联反应制备，最终通过去保护反应得到。关键中间体6-氯-7-脱氮嘌呤2'-C-甲基-β-D-核糖呋喃苷通过具有立体选择性的核碱基负离子糖基化与对甲苯基保护的1,2-脱氧-2'-C-甲基核糖呋喃糖制备而成。1,2-脱氧糖在3步合成，起始原料为易得的2-C-甲基核糖内酯。6-氯-7-脱氮嘌呤阿拉伯呋喃苷中间体通过从3′,5′-保护的6-氯-7-脱氮嘌呤核糖苷经2'-羟基氧化再还原而获得。所有制备的化合物均未显示出明显的细胞毒性或抗病毒活性。