2-C-methyl-3,5-di-O-(4-methylbenzoyl)-D-ribofuranose | 943638-20-8

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 芳香烃
• 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: 2-C-methyl-3,5-di-O-(4-methylbenzoyl)-D-ribofuranose
• 英文别名: 3,5-bis-O-(4-methylbenzoyl)-2-C-methyl-ribofuranose；2-C-methyl-3,5-di-O-(p-toluoyl)-D-ribofuranose；3,5-di-O-p-toluoyl-2-C-methyl-D-ribofuranose；3,5-di-O-toluoyl-2-C-methyl-D-ribofuranose；[(2R,3R,4R)-4,5-dihydroxy-4-methyl-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
• CAS: 943638-20-8
• 化学式: C₂₂H₂₄O₇
• 分子量: 400.428
• InChiKey: HEHGVXRSPLTBLD-QVUFTONESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 储存条件：
  存储条件：2-8°C，干燥且密封。

反应信息

• 作为反应物：
  描述：

  2-C-methyl-3,5-di-O-(4-methylbenzoyl)-D-ribofuranose 在 N,N-二甲基乙酰胺 、 sodium hydride 、 甲基磺酰氯 、 正丁胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 10.67h， 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：

  在 palladium on activated charcoal 过碘酸 、 盐酸 、 醋酸异丙酯 、 二异丙胺 、 氢气 作用下， 以 水 、 甲醇 为溶剂， 50.0 ℃ 、310.26 kPa 条件下， 反应 24.5h， 以4.03 kg的产率得到2-C-methyl-3,5-di-O-(4-methylbenzoyl)-D-ribofuranose
  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

文献信息

• METHODS FOR TREATING HCV
  申请人：Delaney William E.

  公开号：US20130273005A1

  公开（公告）日：2013-10-17

  This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.

  这项发明涉及治疗丙型肝炎病毒感染的治疗分子组合。本发明涉及方法、用途、给药方案和组合物。
• [EN] 1'-SUBSTITUTED-CARBA-NUCLEOSIDE PRODRUGS FOR ANTIVIRAL TREATMENT<br/>[FR] PROMÉDICAMENTS CARBA-NUCLÉOSIDES 1'-SUBSTITUÉS POUR TRAITEMENT ANTIVIRAL
  申请人：GILEAD SCIENCES INC

  公开号：WO2011150288A1

  公开（公告）日：2011-12-01

  Provided are prodrugs of pyrrolo[l,2-f][l,2,4]triazin-7-yl nucleoside phosphates wherein the 1 ' position of the nucleoside sugar is substituted with CN. The compounds, compositions, and methods provided are useful for the treatment Hepatitis C infections.

  提供了吡咯并[1,2-f][1,2,4]三氮杂七基核苷酸的前药，其中核苷糖的1'位置被CN取代。所提供的化合物、组合物和方法对治疗丙型肝炎感染是有用的。
• [EN] 5'-SUBSTITUTED NUCLEOSIDE ANALOGS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES<br/>[FR] ANALOGUES DE NUCLÉOSIDES 5'-SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION POUR LE TRAITEMENT DE MALADIES VIRALES
  申请人：MERCK SHARP & DOHME

  公开号：WO2013009737A1

  公开（公告）日：2013-01-17

  The present invention relates to 5'-Substituted Nucleoside Analogs of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, Z, R1, R2, R3 and R3' are as defined herein. The present invention also relates to compositions comprising at least one 5'-Substituted Nucleoside Analog, and methods of using the 5'-Substituted Nucleoside Analogs for treating or preventing HCV infection in a patient.

  本发明涉及式(I)的5'-取代核苷类似物及其药用盐，其中B、X、Z、R1、R2、R3和R3'如本文所定义。本发明还涉及包含至少一种5'-取代核苷类似物的组合物，以及使用这些5'-取代核苷类似物治疗或预防患者HCV感染的方法。
• [EN] CARBA-NUCLEOSIDE ANALOGS FOR ANTIVIRAL TREATMENT<br/>[FR] ANALOGUES DE CARBA-NUCLÉOSIDE POUR UN TRAITEMENT ANTIVIRAL
  申请人：GILEAD SCIENCES INC

  公开号：WO2009132123A1

  公开（公告）日：2009-10-29

  Provided are imidazol [1,5-f] [1,2.4]triazinyl, imidazol [1,2,4]triazinyl, and [1,2,4] triazolo [4,3-f] [1,2,4] triazinyl nucleosides of formula I nucleoside phosphates and prodrugs thereof. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections, particularly hepatitis C infections. Wherein X1 or X2 is indepently C-R10 or N and wherein at least one of X1 or X2 is N.

  提供的是式I核苷酸磷酸酯和其前药，包括咪唑[1,5-f][1,2.4]三唑基、咪唑[1,2,4]三唑基和[1,2,4]三唑[4,3-f][1,2,4]三唑基。所提供的化合物、组合物和方法对于治疗黄病毒科病毒感染，特别是丙型肝炎感染，具有益处。其中X1或X2独立地为C-R10或N，且至少其中之一为N。
• 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。