ethyl (2R,3R)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-fluoro-2-methyl-3-sulfooxypropanoate | 1020063-92-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (2R,3R)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-fluoro-2-methyl-3-sulfooxypropanoate
• CAS: 1020063-92-6
• 化学式: C₁₁H₁₉FO₈S
• 分子量: 330.331
• InChiKey: XRFULEACXKRTDI-SOCHQFKDSA-N

物化性质

• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl (2R,3R)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-fluoro-2-methyl-3-sulfooxypropanoate 在 盐酸 、 水 、 2,2-二甲氧基丙烷 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 (2R,3R)-ethyl-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluoro-2-methyl-3-hydroxy propionate
  参考文献：
  名称：

  An Efficient and Diastereoselective Synthesis of PSI-6130: A Clinically Efficacious Inhibitor of HCV NS5B Polymerase

  摘要：

  R7128 is the prodrug of 2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130), a potent and selective inhibitor of HCV NS5B polymerase. Currently, R7128 is in clinical trials for the treatment of HCV infection. To support clinical development efforts, we needed an efficient and scalable synthesis of PSI-6130. We describe an improved, diastereoselective synthetic route starting with protected D-glyceraldehyde. No chiral reagents or catalysts were used to produce the three new contiguous stereocenters. Introduction of fluorine at the C-2 tertiary carbon was accomplished in a highly regio- and stereoselective manner through nucleophilic substitution oil a cyclic sulfate. Scale-limiting chromatographic purifications were eliminated through the use of crystalline intermediates.

  DOI：

  10.1021/jo901345j
• 作为产物：
  描述：

  (4S,5R)-5-((R)-2,2-二甲基-1,3-二氧戊环-4-基)-4-甲基-1,3 在 Tetraethylammonium fluoride dihydrate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 ethyl (2R,3R)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-fluoro-2-methyl-3-sulfooxypropanoate
  参考文献：
  名称：

  An Efficient and Diastereoselective Synthesis of PSI-6130: A Clinically Efficacious Inhibitor of HCV NS5B Polymerase

  摘要：

  R7128 is the prodrug of 2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130), a potent and selective inhibitor of HCV NS5B polymerase. Currently, R7128 is in clinical trials for the treatment of HCV infection. To support clinical development efforts, we needed an efficient and scalable synthesis of PSI-6130. We describe an improved, diastereoselective synthetic route starting with protected D-glyceraldehyde. No chiral reagents or catalysts were used to produce the three new contiguous stereocenters. Introduction of fluorine at the C-2 tertiary carbon was accomplished in a highly regio- and stereoselective manner through nucleophilic substitution oil a cyclic sulfate. Scale-limiting chromatographic purifications were eliminated through the use of crystalline intermediates.

  DOI：

  10.1021/jo901345j

文献信息

• (2R)-2-DEOXY-2,2-DISUBSTITUTED-RIBONO-1,4-LACTONE AND PREPARATION METHOD AND USE THEREOF
  申请人：TOPHARMAN SHANGHAI CO., LTD.

  公开号：US20150284351A1

  公开（公告）日：2015-10-08

  This invention disclose (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone in a single configuration and preparation method and use thereof. The (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone, or a pharmaceutically acceptable salt, an ester, a prodrug or a solvate thereof according to the invention are important intermediates of a variety of anti-viral and anti-tumor active ingredients. A compound obtained from (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone via an acylation reaction can be directly used for preparing various anti-viral and anti-tumor drugs. The Chiral synthesis method and the spontaneous resolution method of the compound of (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone according to the invention have the following advantages: the reaction routes are short and simple with high yield and low cost, which are suitable for industrial application.

  这项发明披露了一种单一构型的(2R)-2-去氧-2,2-二取代核糖酮-1,4-内酯及其制备方法和用途。根据该发明，所述的(2R)-2-去氧-2,2-二取代核糖酮-1,4-内酯，或其药学上可接受的盐、酯、前药或溶剂化合物是多种抗病毒和抗肿瘤活性成分的重要中间体。通过酰化反应从(2R)-2-去氧-2,2-二取代核糖酮-1,4-内酯获得的化合物可以直接用于制备各种抗病毒和抗肿瘤药物。根据该发明，(2R)-2-去氧-2,2-二取代核糖酮-1,4-内酯的手性合成方法和自发分辨方法具有以下优点：反应路线短且简单，产率高，成本低，适合工业应用。
• PREPARATION OF NUCLEOSIDES RIBOFURANOSYL PYRIMIDINES
  申请人：Axt Steven D.

  公开号：US20100056770A1

  公开（公告）日：2010-03-04

  The present process provides an improved method for the preparation of 4-amino-1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydrox-ymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one of the formula (IV) which is a potent inhibitor of Hepatitis C Virus (HCV) NS5B polymerase.

  本发明提供了一种改进的方法，用于制备式（IV）的4-氨基-1-((2R,3R,4R,5R)-3-氟-4-羟基-5-羟基甲基-3-甲基-四氢呋喃-2-基)-1H-嘧啶-2-酮，该化合物是丙型肝炎病毒（HCV）NS5B聚合酶的有效抑制剂。
• Preparation of nucleosides ribofuranosyl pyrimidines
  申请人：Axt Steven D.

  公开号：US20080139802A1

  公开（公告）日：2008-06-12

  The present process provides an improved method for converting 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactones derivatives to 3-fluoro-3-methyl-2-chlorofuran compounds which are useful for the synthesis of nucleosides and improved processes for the synthesis of the D-ribonolactone compounds.

  本方法提供了一种改进的方法，用于将2'-脱氧-2'-氟-2'-甲基-D-核糖内酯衍生物转化为有用于核苷合成的3-氟-3-甲基-2-氯呋喃化合物，以及合成D-核糖内酯化合物的改进过程。
• [EN] (2R)-2-DEOXY-2,2-DISUBSTITUTE-1,4-RIBOSE LACTONE AND PREPARATION METHOD AND USE THEREOF<br/>[FR] (2R)-2-DÉSOXY-1,4-LACTONE-RIBOSE 2,2-DISUBSTITUÉ ET PROCÉDÉ DE PRÉPARATION ET UTILISATION DE CELUI-CI
  申请人：TOPHARMAN SHANGHAI CO LTD

  公开号：WO2014056442A1

  公开（公告）日：2014-04-17

  本发明公开了一种单一构型的（2R）-2-脱氧-2，2-二取代-1，4-核糖内酯及其制备方法和用途。本发明提供的下述通式V表示的（2R）-2-脱氧-2，2-二取代-1，4-核糖内酯或其药学上可接受的盐、酯、前药或溶剂合物，其为多种抗病毒、抗肿瘤活性成分的重要中间体。通过通式（V）表示的化合物的酰化反应获得通式（VI）表示的化合物可以直接用于制备多种抗病毒、抗肿瘤的药物。本发明提供的通式（V）表示的化合物的手性合成方法和结晶化拆分方法具有以下优点：路线短、方法简便、收率高、成本低、适于工业化生产。
• US8912321B2
  申请人：——

  公开号：US8912321B2

  公开（公告）日：2014-12-16