1-O-methyl-2,3,5-tri-O-benzoyl-L-lyxofuranose | 169529-25-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-O-methyl-2,3,5-tri-O-benzoyl-L-lyxofuranose
• 英文别名: methyl 2,3,5-tri-O-benzoyl-L-lyxofuranoside；1-O-methyl-2,3,5-tri-O-benzoyl-L-lyxose；[(2S,3R,4R)-3,4-dibenzoyloxy-5-methoxyoxolan-2-yl]methyl benzoate
• CAS: 169529-25-3
• 化学式: C₂₇H₂₄O₈
• 分子量: 476.483
• InChiKey: XJKNQPQTQXKNOC-RYMFGWHHSA-N

物化性质

• 沸点：
  598.8±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  97.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-O-methyl-2,3,5-tri-O-benzoyl-L-lyxofuranose 在 盐酸 、 硝基甲烷 、 硫酸 、 三氟化硼乙醚 、 sodium methylate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 丙酮 为溶剂， 反应 26.0h， 生成 3-bromo-4-N-trimethylacetylamino-1-(2,3-O-isopropylidene-α-L-lyxofuranosyl)pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 3. Synthesis, SAR, and Antiinflammatory Activity of a Series of l-Lyxofuranosyl Nucleosides

  摘要：

  Chronic inflammatory diseases, such as arthritis and rheumatoid arthritis, remain major health problems worldwide. We previously demonstrated that adenosine kinase inhibitors (AKIs) exhibit antiinflammatory effects by inhibiting TNF-alpha production, neutrophil accumulation, and edema formation. Although adenosine receptor agonists produce similar effects, AKIs showed the antiinflammatory activity without the cardiovascular side effects that prevented the development of adenosine receptor specific agonists. However, previously described potent AKIs, such as 5-iodotubercidin, are nucleosides which have the potential to undergo in vivo 5'-O-phosphorylation and therefore produce cytotoxicity. In an effort to eliminate toxicities produced by phosphorylated nucleosides, L-lyxofuranosyl analogues of tubercidin were tested as potential AKIs since the opposite stereochemical. orientation of the CH2OH was expected to eliminate intracellular phosphorylation. Described herein are the discovery of a new series of AKIs based on alpha-L-lyxofuranosyl. nucleosides, their SAR, as well as the antiinflammatory activity of the lead compound GP790 (IC50 = 0.47 nM, 47% inhibition of paw swelling at 10 mg/kg in rat carrageenan paw edema model). In addition, a study showing that in the skin lesion model the antiinflammatory activity is reversed by an A2 selective adenosine receptor antagonist 3,7-dimethyl-1-propylxanthine (DMPX) is also described.

  DOI：

  10.1021/jm030230z
• 作为产物：
  描述：

  苯甲酸酐 、 methyl L-lyxofuranoside 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 反应 16.0h， 以47 g的产率得到1-O-methyl-2,3,5-tri-O-benzoyl-L-lyxofuranose
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 3. Synthesis, SAR, and Antiinflammatory Activity of a Series of l-Lyxofuranosyl Nucleosides

  摘要：

  Chronic inflammatory diseases, such as arthritis and rheumatoid arthritis, remain major health problems worldwide. We previously demonstrated that adenosine kinase inhibitors (AKIs) exhibit antiinflammatory effects by inhibiting TNF-alpha production, neutrophil accumulation, and edema formation. Although adenosine receptor agonists produce similar effects, AKIs showed the antiinflammatory activity without the cardiovascular side effects that prevented the development of adenosine receptor specific agonists. However, previously described potent AKIs, such as 5-iodotubercidin, are nucleosides which have the potential to undergo in vivo 5'-O-phosphorylation and therefore produce cytotoxicity. In an effort to eliminate toxicities produced by phosphorylated nucleosides, L-lyxofuranosyl analogues of tubercidin were tested as potential AKIs since the opposite stereochemical. orientation of the CH2OH was expected to eliminate intracellular phosphorylation. Described herein are the discovery of a new series of AKIs based on alpha-L-lyxofuranosyl. nucleosides, their SAR, as well as the antiinflammatory activity of the lead compound GP790 (IC50 = 0.47 nM, 47% inhibition of paw swelling at 10 mg/kg in rat carrageenan paw edema model). In addition, a study showing that in the skin lesion model the antiinflammatory activity is reversed by an A2 selective adenosine receptor antagonist 3,7-dimethyl-1-propylxanthine (DMPX) is also described.

  DOI：

  10.1021/jm030230z

文献信息

• SYNTHETIC INTERMEDIATE OF 1-(2-DEOXY-2-FLUORO-4-THIO-ß-D-ARABINOFURANOSYL)CYTOSINE, SYNTHETIC INTERMEDIATE OF THIONUCLEOSIDE, AND METHOD FOR PRODUCING THE SAME
  申请人：FUJIFILM Corporation

  公开号：US20150152131A1

  公开（公告）日：2015-06-04

  A compound represented by a formula [1D] as shown below (wherein R 1A , R 1B , R 2A , R 2B , R 3A and R 3B represent a hydrogen atom, an optionally substituted C 1-6 alkyl group, and the like) is useful as an intermediate for producing a thionucleoside, and the production method of the present invention is useful as a method for producing a thionucleoside.

  下列的化合物，其化学式为[1D]（其中R1A、R1B、R2A、R2B、R3A和R3B代表氢原子、可选择取代的C1-6烷基等），可作为生产硫代核苷的中间体，本发明的生产方法可作为一种生产硫代核苷的方法。
• SYNTHESIS OF FOUR ESTER PROTECTED THIOFURANOSE SUGARS
  作者：Ian Birtwistle、Peter Maddocks、John M. O'Callaghan、John Warren

  DOI：10.1081/scc-100108233

  日期：2001.1.1

  The products obtained by titanium tetrachloride mediated dithioacetalization of four pentofuranoside derivatives were converted to thiofuranose sugars, either by direct cyclization via the unstable triflate intermediate, or by treatment of the derived mesylate. A facile inversion of a D-ribose dibenzyl dithioacetal 9 to an L-lyxose dibenzyl dithioacetal 12 via hydrolysis of the Mitsunobu derived formate

  通过四氯化钛介导的四种呋喃戊糖苷衍生物的二硫代缩醛化获得的产物通过不稳定的三氟甲磺酸酯中间体直接环化或通过处理衍生的甲磺酸酯转化为硫代呋喃糖。还描述了通过水解 Mitsunobu 衍生的甲酸酯中间体，将 D-核糖二苄基二硫缩醛 9 轻松转化为 L-来苏糖二苄基二硫缩醛 12。
• １−（２−デオキシ−２−フルオロ−４−チオ−β−Ｄ−アラビノフラノシル）シトシンの合成中間体およびチオヌクレオシドの合成中間体ならびにそれらの製造法
  申请人：富士フイルム株式会社

  公开号：WO2014027658A1

  公开（公告）日：2014-02-20

  下記一般式［１Ｄ］（式中、Ｒ１Ａ、Ｒ１Ｂ、Ｒ２Ａ、Ｒ２Ｂ、Ｒ３ＡおよびＲ３Ｂは水素原子、置換されてもよいＣ１−６アルキル基などを示す。）で表される化合物は、チオヌクレオシドを製造するための中間体として有用であり、本発明の製造法はチオヌクレオシドの製造法として有用である。

  下列一般式［１Ｄ］（式中，Ｒ１Ａ、Ｒ１Ｂ、Ｒ２Ａ、Ｒ２Ｂ、Ｒ３Ａ和Ｒ３Ｂ表示氢原子，可取代的C1-6烷基等。）所表示的化合物，是作为制造硫代核苷的中间体而有用的，本发明的制造方法是制造硫代核苷的方法，因此具有实用性。
• INTERMEDIATE FOR SYNTHESIS OF 1-(2-DEOXY-2-FLUORO-4-THIO-beta-D-ARABINOFURANOSYL) CYTOSINE, INTERMEDIATE FOR SYNTHESIS OF THIONUCLEOSIDE, AND METHODS FOR PRODUCING THESE INTERMEDIATES
  申请人：FUJIFILM Corporation

  公开号：EP2883866A1

  公开（公告）日：2015-06-17

  A compound represented by a formula [ID] as shown below (wherein R1A, R1B, R2A, R2B, R3A and R3B represent a hydrogen atom, an optionally substituted C1-6 alkyl group, and the like) is useful as an intermediate for producing a thionucleoside, and the production method of the present invention is useful as a method for producing a thionucleoside.

  由下式[ID]表示的化合物（其中 R1A、R1B、R2A、R2B、R3A 和 R3B 代表氢原子、任选取代的 C1-6 烷基等）可用作生产硫代核苷的中间体，本发明的生产方法可用作生产硫代核苷的方法。
• SYNTHETIC INTERMEDIATE OF 1-(2-DEOXY-2-FLUORO-4-THIO-SS-D-ARABINOFURANOSYL)CYTOSINE
  申请人：Fujifilm Corporation

  公开号：EP3184112A1

  公开（公告）日：2017-06-28

  Synthetic intermediate of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine A compound represented by the formula [1F]: wherein R1 represents a hydrogen atom or a hydroxyl protecting group; R2 represents a hydrogen atom or a hydroxyl-protecting group; R3C represents a hydrogen atom, a halogen atom, an optionally substituted alkyl group or -OR3a corresponding to a hydroxyl-protecting group; R3D represents a hydrogen atom, a halogen atom, an optionally substituted alkyl group or -OR3a corresponding to a hydroxyl-protecting group; R4 represents a halogen atom, a hydroxyl group, an optionally substituted alkylsulfonyloxy group or an optionally substituted arylsulfonyloxy group; R5 and R6 together represent =O or =NOR7 wherein R7 represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted silyl group; or R4 and R5 together represent a sulfur atom; and R6 represents a hydroxyl group. The compound is useful as an intermediate for producing a thionucleoside.

  1-(2-脱氧-2-氟-4-硫代-β-D-阿拉伯呋喃糖基)胞嘧啶的合成中间体 由式[1F]表示的化合物： 其中 R1 代表氢原子或羟基保护基团； R2 代表氢原子或羟基保护基团； R3C 代表氢原子、卤素原子、任选取代的烷基或与羟基保护基团相对应的-OR3a； R3D 代表氢原子、卤素原子、任选取代的烷基或与羟基保护基团相对应的-OR3a；R4 代表卤原子、羟基、任选取代的烷基磺酰氧基或任选取代的芳基磺酰氧基；R5 和 R6 共同代表 =O 或 =NOR7 其中 R7 代表氢原子、任选取代的烷基、任选取代的芳基、任选取代的杂环基或任选取代的硅基；或 R4 和 R5 共同代表硫原子；R6 代表羟基。该化合物可用作生产硫代核苷的中间体。