(3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-carbaldehyde | 70722-99-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-carbaldehyde
• 英文别名: (3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde；3-Desoxy-3-fluor-1,2-O-isopropyliden-α-D-xylo-pentodialdofuranose；(3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde
• CAS: 70722-99-5
• 化学式: C₈H₁₁FO₄
• 分子量: 190.171
• InChiKey: YMYWHCUMGSTCLF-XZBKPIIZSA-N

物化性质

• 沸点：
  232.6±40.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-carbaldehyde 在 sodium tetrahydroborate 、 乙醇 、 三氟甲磺酸三甲基硅酯 、 硫酸 、 氨 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 35.5h， 生成 (2R,3S,4R,5R)-2-(6-amino-9H-purin-9-yl)-4-fluoro-5-(hydroxymethyl)tetrahydrofuran-3-ol
  参考文献：
  名称：

  核苷化合物的氨基磷酸酯衍生物及其用途

  摘要：

  本发明属于药物技术领域，涉及核苷化合物的氨基磷酸酯衍生物及其用途，以及包含该类化合物的药物组合物，它们可以作为抗病毒试剂，尤其是抗新型冠状病毒(SARS‑CoV‑2)试剂。本发明还涉及制备这类化合物和药物组合物的方法，以及它们在预防或治疗病毒感染，包括但不限于，黄病毒科病毒感染、丝状病毒科病毒感染、肠道病毒科病毒感染、正粘液病毒科病毒感染、副粘液病毒科病毒感染、冠状病毒科病毒感染，特别是新型冠状病毒(SARS‑CoV‑2)感染中的用途。

  公开号：

  CN112010916B
• 作为产物：
  描述：

  1,2:5,6-di-O-isopropylidene-3-O-trifluoromethanesulfonyl-α-D-allofuranose 在 sodium periodate 、 硫酸 、 cesium fluoride 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 叔丁醇 为溶剂， 反应 47.0h， 生成 (3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-carbaldehyde
  参考文献：
  名称：

  3-Fluoroazetidinecarboxylic Acids and trans,trans-3,4-Difluoroproline as Peptide Scaffolds: Inhibition of Pancreatic Cancer Cell Growth by a Fluoroazetidine Iminosugar

  摘要：

  Reverse aldol opening tenders amides of 3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above pH 8. Axe, found in sugar beet, is mis-incorporated for proline in peptides in humans and is associated with multiple sclerosis and teratogenesis. Axe-containing peptides may be oxygenated by prolyl hydroxylases resulting in potential damage of the protein by a reverse aldol of the hydroxyazetidine; this, rather than changes in conformation; may account for the deleterious effects of Axe. This paper describes the synthesis of 3-fluoro-Aze amino acids as hydroxy-Aze analogues which are not susceptible to aldol cleavage. 4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building blocks. trans,trans-2,4-dihydroxy-3-fluoroazetidine, an iminosugar, inhibits the growth of pancreatic cancer cells to a similar degree as gemcitabine.

  DOI：

  10.1021/acs.joc.5b00463

文献信息

• TLR7 AGONISTS
  申请人：Primmune Therapeutics, Inc.

  公开号：US20210155652A1

  公开（公告）日：2021-05-27

  The present invention relates to TLR7 agonists according to Formula I and their use in the treatment of diseases such as cancer and infectious disease.

  本发明涉及根据式I的TLR7激动剂及其在治疗癌症和传染病等疾病中的应用。
• l-DMDP, l-homoDMDP and their C-3 fluorinated derivatives: synthesis and glycosidase-inhibition
  作者：Yi-Xian Li、Mu-Hua Huang、Yukiko Yamashita、Atsushi Kato、Yue-Mei Jia、Wu-Bao Wang、George W. J. Fleet、Robert J. Nash、Chu-Yi Yu

  DOI：10.1039/c0ob01063d

  日期：——

  L-DMDP and L-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from D-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While L-DMDP and L-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.

  L-DMDP和L-homoDMDP是天然存在的DMDP和homoDMDP的对映体，已通过从D-木糖衍生的环状亚硝酮9合成。它们的3-去氧-3-氟化类似物也通过从氟化糖12经过七步反应制备的多羟基氟化环状亚硝酮10获得。这些亚氨糖对多种糖苷酶的生物活性进行了评估。虽然L-DMDP和L-homoDMDP是α-葡萄糖苷酶的强抑制剂，但当这些化合物的C-3羟基被氟替代时，抑制作用明显下降，这显示了C-3羟基在与酶相互作用中的重要性。
• Synthesis of Non‐Classical Arylated C‐Saccharides through Nickel/Photoredox Dual Catalysis
  作者：Audrey Dumoulin、Jennifer K. Matsui、Álvaro Gutiérrez‐Bonet、Gary A. Molander

  DOI：10.1002/anie.201802282

  日期：2018.5.28

  synthetic tools to introduce saccharide derivatives into functionally complex molecules is of great interest, particularly in the field of drug discovery. Herein, we report a new route toward highly functionalized, arylated saccharides, which involves nickel‐catalyzed cross‐coupling of photoredox‐generated saccharyl radicals with a range of aryl‐ and heteroaryl bromides, triggered by an organic photocatalyst

  将糖衍生物引入功能复杂的分子中的合成工具的开发引起了极大的兴趣，特别是在药物发现领域。本文中，我们报告了一条通往高功能化，芳基化糖类的新途径，其中涉及由有机光催化剂引发的镍催化的光氧化还原产生的糖基与一系列芳基和杂芳基溴化物的交叉偶联。与现有方法相反，温和的反应条件实现了糖基序的芳基化，同时保留了异头碳，因此提供了一种至今仍未得到充分研究的芳基化糖苷。为了证明该策略在后期功能化中的潜力，合成了多种结合糖部分的结构复杂的分子。
• Study on fluorination-toxicity relationships. Syntheses of 1-N-[(2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl] derivatives of kanamycins
  作者：Yoshiaki Takahashi、Chiga ueda、Tsutomu Tsuchiya、Yoshihiko Kobayashi

  DOI：10.1016/0008-6215(93)84060-j

  日期：1993.10

  (2R,3R)- And (2R,3S)-4-azido-3-fluoro-2-hydroxybutanoic acids (11 and 22) have been prepared from 3-deoxy-3-fluoro-1,2-0-isopropylidene-a-D-glucofuranose (1) and 3,5-di-O-benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose (12), respectively. They were then coupled to the H2N-1 group of suitably protected kanamycin A or kanamycin B analogs to give, 1-N-[(2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl]kanamycins (32-35). This group of compounds (32-34) exhibited similar antibacterial activity and toxicity level as those of the corresponding 1-N-[(S)-4-amino-2-hydroxybutanoyl] (AHB) derivatives of kanamycins. The base strength of the H2N-4''' group of 32 and 34, as determined by C-13 NMR spectroscopy (in D2O) at varying pD values, was found to be lower when compared to the basicity for the corresponding AHB analogs. The relationship between observed toxicity and base strength of the H2N-4''' group is discussed.

  (2R,3R)-和(2R,3S)-4-叠氮-3-氟-2-羟基丁酸(11和22)分别由3-去氧-3-氟-1,2-O-异丙叉基-a-D-古洛吡喃糖(1)和3,5-二-O-苯甲基-1,2-O-异丙叉基-a-D-木糖吡喃糖(12)制备。随后，它们被连接到适当保护的卡那霉素A或卡那霉素B类似物的H2N-1基团上，生成1-N-[(2R,3R)-和(2R,3S)-4-氨基-3-氟-2-羟基丁酰]卡那霉素(32-35)。该类化合物(32-34)表现出与卡那霉素对应1-N-[(S)-4-氨基-2-羟基丁酰](AHB)衍生物相似的抗菌活性和毒性水平。通过C-13核磁共振光谱(在D2O中，不同pD值测定)，H2N-4'''基团(32和34)的碱性强弱与对应的AHB类似物相比较低。观察到的毒性和H2N-4'''基团的碱强度之间的关系进行了讨论。
• Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position
  作者：Stanislaw F. Wnuk、Jenay Robert、Adam J. Sobczak、Brandon P. Meyers、Venkata L.A. Malladi、Jinge Zhu、Bhaskar Gopishetty、Dehua Pei

  DOI：10.1016/j.bmc.2009.07.057

  日期：2009.9

  S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether bond of S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), which is the precursor of type 2 autoinducer for bacterial cell-cell communication. In this work, we have synthesized several SRH analogues modi. ed at the ribose C3 position as potential inhibitors of LuxS. While removal or methylation of the C3-OH resulted in simple competitive inhibitors of moderate potency, inversion of the C3 stereochemistry or substitution of. uorine for C3-OH resulted in slow-binding inhibitors of improved potency. The most potent inhibitor showed a K*(I) value of 0.43 mu M. (C) 2009 Elsevier Ltd. All rights reserved.