5-benzyloxy-2-desoxy-3-hydroxy-D-ribonolactone | 95504-02-2

• 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: 5-benzyloxy-2-desoxy-3-hydroxy-D-ribonolactone
• 英文别名: (4S,5R)-5-((benzyloxy)methyl)-4-hydroxydihydrofuran-2(3H)-one；5-benzyloxy-2-desoxy-3-hydroxy-D-arabinolactone；(4S,5R)-4-hydroxy-5-(phenylmethoxymethyl)oxolan-2-one
• CAS: 95504-02-2
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: QXRWHLQQDHCDBY-WDEREUQCSA-N

物化性质

• 沸点：
  410.6±35.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-benzyloxy-2-desoxy-3-hydroxy-D-ribonolactone 在 咪唑 、 4-二甲氨基吡啶 、 二异丁基氢化铝 、 N-氟代双苯磺酰胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 27.67h， 生成 (3S,4R,5R)-5-(benzyloxymethyl)-3-fluoro-4-(triisopropylsilyloxy)tetrahydrofuran-2-ol
  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
• 作为产物：
  描述：

  3-苄氧基丙醛 在 二异丙氧基二氯化钛 、 CHF₃O₃S*C₁₃H₁₈N₂O 、 三氟化硼乙醚 、 水 、 三氟乙酸 、 copper dichloride 、 锌 作用下， 以 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 96.0h， 生成 5-benzyloxy-2-desoxy-3-hydroxy-D-ribonolactone
  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

• Synthesis and evaluation of 2′-dihalo ribonucleotide prodrugs with activity against hepatitis C virus
  作者：A. Chris Krueger、Hui-Ju Chen、John T. Randolph、Brian S. Brown、Geoff T. Halvorsen、Howard R. Heyman、Tongmei Li、Christopher C. Marvin、Jason P. Shanley、Eric A. Voight、Daniel A.J. Bow、Cecilia Van Handel、Vincent Peterkin、Robert A. Carr、DeAnne Stolarik、Tatyana Dekhtyar、Michelle L. Irvin、Preethi Krishnan、Rodger F. Henry、Rolf Wagner、David A. DeGoey

  DOI：10.1016/j.bmc.2019.115208

  日期：2020.1

  class. Our investigations focused on several potent 2'-halogenated uridine-based HCV polymerase inhibitors, resulting in the discovery of novel 2'-deoxy-2'-dihalo-uridine analogs that are potent inhibitors in replicon assays for all genotypes. Further studies to improve in vivo performance of these nucleoside inhibitors identified aminoisobutyric acid ethyl ester (AIBEE) phosphoramidate prodrugs 18a and

  丙型肝炎病毒（HCV）核苷抑制剂已成为近二十年来HCV药物研究的重点，这是由于此类药物中的分子对药物耐药性和泛基因型活性谱具有很高的障碍。我们的研究集中在几种有效的基于2'-卤代尿苷的HCV聚合酶抑制剂，从而发现了新颖的2'-脱氧-2'-二卤代尿苷类似物，它们在所有基因型的复制子测定中均是有效的抑制剂。为了改善这些核苷抑制剂的体内性能而进行的进一步研究确定了氨基异丁酸乙酯（AIBEE）氨基磷酸亚磷酸酯前药18a和18c，它们在犬肝中提供了高水平的活性三磷酸酯。将AIBEE前药18c与sofosbuvir（1）进行比较，方法是在狗中口服共同给药这两种化合物（每只5 mg / kg），并在给药后4和24小时测量肝中活性三磷酸代谢物的浓度。在这项研究中，在两个活检时间点，18c提供的肝脏三磷酸浓度均比sofosbuvir（1）高6倍，这表明18c可能是临床上治疗HCV感染患者的高效药物。
• [EN] OLIGONUCLEOTIDES WITH 2'-DEOXY-2'-F-2'-C-METHYL NUCLEOTIDES<br/>[FR] OLIGONUCLÉOTIDES À NUCLÉOTIDES 2'-DÉSOXY-2'-F-2'-C-MÉTHYLE
  申请人：[en]ALNYLAM PHARMACEUTICALS, INC.

  公开号：WO2023069495A1

  公开（公告）日：2023-04-27

  The present disclosure relates generally to 2'-geminal substituted nucleosides and nucleotides, and oligonucleotides and dsRNA molecules comprising such 2'-geminal substituted nucleosides and nucleotides.