(3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-one | 1040882-61-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-one
• 英文别名: 2-fluoro-2-C-methyl-D-ribono-γ-lactone；(3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one
• CAS: 1040882-61-8
• 化学式: C₆H₉FO₄
• 分子量: 164.133
• InChiKey: VNCJYMKHJWVTPK-KODRXGBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-one 、 N-[(S)-(2,3,4,5,6-五氟苯氧基)苯氧基磷酰基]-L-丙氨酸异丙酯 在 吡啶 、 二甲基氯化铝 作用下， 以 正己烷 为溶剂， 反应 19.0h， 以99.588%的产率得到
  参考文献：
  名称：

  Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189

  摘要：

  A general and efficient method for the synthesis of pronucleotide (ProTide) 5'-phosphoramidate monoesters is :reported. This method consists of a highly stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing, 3'-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.

  DOI：

  10.1021/acs.orglett.7b00469
• 作为产物：
  描述：

  S-phenyl (3R)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-fluoro-3-hydroxy-2-methylpropanethioate 在 水 、 溶剂黄146 作用下， 反应 5.0h， 生成 核苷类中间体 、 (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-one
  参考文献：
  名称：

  NOVEL PROCESS FOR THE PREPARATION OF (2R)-2-DEOXY-2-FLUORO-2-METHYL-D-ERYTHRO-PENTONO-GAMMA-LACTONE AND (2S)-2-DEOXY-2-FLUORO-2-METHYL-D-ERYTHRO-PENTONO-GAMMA-LACTONE

  摘要：

  本发明提供了制备化合物（2R）-2-去氧-2-氟-2-甲基-D-赤霉糖-γ-内酯（11）和（2S）-2-去氧-2-氟-2-甲基-D-赤霉糖-γ-内酯（12）的新方法，这些是制备关键中间体3,5-二-O-酰基-2-氟-2-C-甲基-D-核糖-γ-内酯（B）的中间体，用于制备1-(2-去氧-2-氟-2-C-甲基-β-D-核糖呋喃核苷)胞嘧啶（A）的方法，该化合物是一种有效的、选择性的抗丙型肝炎病毒药物。

  公开号：

  US20080177079A1

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 alkyl-substituted 2-deoxy-2-fluoro-D-ribofuranosyl pyrimidines and purines and their derivatives
  申请人：Wang Peiyuan

  公开号：US20060199783A1

  公开（公告）日：2006-09-07

  The present invention provides (i) a process for preparing a 2-deoxy-2-fluoro-2-methyl-D-ribonolactone derivative, (ii) conversion of the lactone to nucleosides with potent anti-HCV activity, and their analogues, and (iii) a method to prepare the anti-HCV nucleosides containing the 2-deoxy-2-fluoro-2-C-methyl-o-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

  本发明提供了(i)一种制备2-去氧-2-氟-2-甲基-D-核糖内酯衍生物的过程，(ii)将内酯转化为具有强效抗HCV活性的核苷和它们的类似物，以及(iii)一种制备含2-去氧-2-氟-2-C-甲基-o-D-核糖呋喃核苷的抗HCV核苷的方法，该方法从预先形成的、最好是自然存在的核苷中进行。
• PREPARATION OF ALKYL-SUBSTITUTED 2-DEOXY-2-FLUORO-D-RIBOFURANOSYL PYRIMIDINES AND PURINES AND THEIR DERIVATIVES
  申请人：Wang Peiyuan

  公开号：US20100234585A1

  公开（公告）日：2010-09-16

  The present invention provides (i) a process for preparing a 2-deoxy-2-fluoro-2-methyl-D-ribonolactone derivative, (ii) conversion of the lactone to nucleosides with potent anti-HCV activity, and their analogues, and (iii) a method to prepare the anti-HCV nucleosides containing the 2-deoxy-2-fluoro-2-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

  本发明提供了：(i) 一种制备2-脱氧-2-氟-2-甲基-D-核糖内酯衍生物的过程，(ii) 将内酯转化为具有强效抗丙型肝炎病毒活性的核苷和它们的类似物，以及(iii) 一种制备含有2-脱氧-2-氟-2-C-甲基-β-D-核糖呋喃核苷的抗丙型肝炎病毒核苷的方法，从预先形成的、最好是自然存在的核苷中。
• Preparation of alkyl-substituted 2-deoxy-2-fluoro-d-ribofuranosyl pyrimidines and purines and their derivatives
  申请人：Pharmasset, Inc.

  公开号：EP2348029A1

  公开（公告）日：2011-07-27

  The present invention provides a method to prepare anti-HCV nucleosides containing the 2-deoxy-2-fluoro-2-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

  本发明提供了一种从预先形成的（最好是天然存在的）核苷中制备含有 2-脱氧-2-氟-2-C-甲基-β-D-呋喃核糖基核苷的抗 HCV 核苷的方法。
• Preparation of 2′-fluoro-2′-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives
  申请人：Gilead Pharmasset LLC

  公开号：US10577359B2

  公开（公告）日：2020-03-03

  The present invention provides (i) processes for preparing a 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-ß-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

  本发明提供了(i)制备2′-脱氧-2′-氟-2′-甲基-D-核糖内酯衍生物的工艺，(ii)将中间内酯转化为具有强效抗HCV活性的核苷、及其类似物，以及(iii)从预成的、最好是天然存在的核苷中制备含有 2′-脱氧-2′-氟-2′-C-甲基-ß-D-呋喃核糖核苷的抗 HCV 核苷的方法。