(4S,5R)-4-hydroxy-5-(hydroxymethyl)-3,3-dimethyldihydrofuran-2(3H)-one | 1214251-87-2

• 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: (4S,5R)-4-hydroxy-5-(hydroxymethyl)-3,3-dimethyldihydrofuran-2(3H)-one
• 英文别名: (4S,5R)-4-hydroxy-5-(hydroxymethyl)-3,3-dimethyloxolan-2-one
• CAS: 1214251-87-2
• 化学式: C₇H₁₂O₄
• 分子量: 160.17
• InChiKey: ZOHHOFVIRZUAHZ-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S,5R)-4-hydroxy-5-(hydroxymethyl)-3,3-dimethyldihydrofuran-2(3H)-one 在 氨 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 12.5h， 生成 (2R)-isopropyl 2-((((5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxy-4,4-dimethyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate
  参考文献：
  名称：

  通过自由能扰动在计算机上设计一种新型核苷酸抗病毒剂

  摘要：

  核苷类似物是抗病毒疗法的支柱。此类药物经过宿主或病毒激酶的加工，形成选择性抑制病毒聚合酶的活性三磷酸核苷。核心假设是三磷酸核苷类似物必须是病毒聚合酶的有利底物，而核苷前体必须是宿主激酶抑制病毒复制的令人满意的底物。进来，自由能扰动（FEP）被用来预测宿主和病毒酶的底物亲和力。本研究使用了几种已知可抑制丙型肝炎病毒 (HCV) 的尿苷 5'-单磷酸前药类似物来验证 FEP 的使用。计算甲基取代的尿苷类似物与宿主单磷酸激酶和病毒 RNA 依赖性 RNA 聚合酶 (RdRp) 的结合自由能。2'-C-甲基-尿苷和 4'-C-甲基-尿苷支架提供了与宿主激酶和 HCV RdRp 的有利底物结合，这与支持我们新方法的细胞抗病毒活性结果一致。在一项前瞻性评估中，FEP 结果表明，2'-C-二甲基尿苷支架分别为宿主激酶和 HCV RdRp 提供了有利的单磷酸盐和三磷酸盐底物。合成了新型 2'-C-二甲基尿苷单磷酸前药，并表现出对

  DOI：

  10.1111/cbdd.14042
• 作为产物：
  描述：

  5-benzyloxy-2-dimethyl-3-hydroxy-D-ribonolactone 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 (4S,5R)-4-hydroxy-5-(hydroxymethyl)-3,3-dimethyldihydrofuran-2(3H)-one
  参考文献：
  名称：

  A General and Enantioselective Approach to Pentoses: A Rapid Synthesis of PSI-6130, the Nucleoside Core of Sofosbuvir

  摘要：

  An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective alpha-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.

  DOI：

  10.1021/ja502205q

文献信息

• NUCLEOSIDE ANALOGUES AND METHODS OF USE THEREOF
  申请人：LCB PHARMA INC.

  公开号：US20190322693A1

  公开（公告）日：2019-10-24

  Nucleoside analogues that can be used as anticancer or antiviral agents are presented. These compounds are nucleoside and/or nucleotide prodrugs. In particular, the subject matter relates to nucleoside analogues comprising a tetrahydrofuranyl, or tetrahydrothienyl moiety which: have a quaternary stereogenic all-carbon center at the 3′ position and bear a phosphoryl group at either one of, or both of positions C5′ and/or C3′; have a quaternary stereogenic all-carbon center at one of the 3′ position, 2′ position, or no quaternary stereogenic center at all, and bear a β-blocked lipoate derivative attached through an amide bond to the primary amine of the nucleobase; or have a quaternary stereogenic all-carbon center at the 2′ position and bear a phosphorylated prodrug at the C5′-position and a β-blocked lipoate derivative attached through an amide bond to the primary amine of the nucleobase.
• US9624183B2
  申请人：——

  公开号：US9624183B2

  公开（公告）日：2017-04-18
• A General and Enantioselective Approach to Pentoses: A Rapid Synthesis of PSI-6130, the Nucleoside Core of Sofosbuvir
  作者：Manuel Peifer、Raphaëlle Berger、Valerie W. Shurtleff、Jay C. Conrad、David W. C. MacMillan

  DOI：10.1021/ja502205q

  日期：2014.4.23

  An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective alpha-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.
• <i>In silico</i> design of a novel nucleotide antiviral agent by free energy perturbation
  作者：Dharmeshkumar Patel、Bryan D. Cox、Mahesh Kasthuri、Seema Mengshetti、Leda Bassit、Kiran Verma、Olivia Ollinger‐Russell、Franck Amblard、Raymond F. Schinazi

  DOI：10.1111/cbdd.14042

  日期：2022.6

  Nucleoside analogs are the backbone of antiviral therapies. Drugs from this class undergo processing by host or viral kinases to form the active nucleoside triphosphate species that selectively inhibits the viral polymerase. It is the central hypothesis that the nucleoside triphosphate analog must be a favorable substrate for the viral polymerase and the nucleoside precursor must be a satisfactory

  核苷类似物是抗病毒疗法的支柱。此类药物经过宿主或病毒激酶的加工，形成选择性抑制病毒聚合酶的活性三磷酸核苷。核心假设是三磷酸核苷类似物必须是病毒聚合酶的有利底物，而核苷前体必须是宿主激酶抑制病毒复制的令人满意的底物。进来，自由能扰动（FEP）被用来预测宿主和病毒酶的底物亲和力。本研究使用了几种已知可抑制丙型肝炎病毒 (HCV) 的尿苷 5'-单磷酸前药类似物来验证 FEP 的使用。计算甲基取代的尿苷类似物与宿主单磷酸激酶和病毒 RNA 依赖性 RNA 聚合酶 (RdRp) 的结合自由能。2'-C-甲基-尿苷和 4'-C-甲基-尿苷支架提供了与宿主激酶和 HCV RdRp 的有利底物结合，这与支持我们新方法的细胞抗病毒活性结果一致。在一项前瞻性评估中，FEP 结果表明，2'-C-二甲基尿苷支架分别为宿主激酶和 HCV RdRp 提供了有利的单磷酸盐和三磷酸盐底物。合成了新型 2'-C-二甲基尿苷单磷酸前药，并表现出对