3-deoxy-3-fluoro-1,2-O-isopropylidene-α-D-glucofuranose | 18530-81-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-deoxy-3-fluoro-1,2-O-isopropylidene-α-D-glucofuranose
• 英文别名: (R)-1-((3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)ethane-1,2-diol；alpha-D-Glucofuranose, 3-deoxy-3-fluoro-1,2-O-(1-methylethylidene)-；(1R)-1-[(3aR,5R,6S,6aS)-6-fluoro-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethane-1,2-diol
• CAS: 18530-81-9
• 化学式: C₉H₁₅FO₅
• 分子量: 222.214
• InChiKey: QFTYRVBAYCTBOA-OZRXBMAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  68.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-deoxy-3-fluoro-1,2-O-isopropylidene-α-D-glucofuranose 在 吡啶 、 2,4,6-三甲基吡啶 、 甲酸 、 二乙胺基三氟化硫 、 水 、 氢溴酸 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 334.33h， 生成 1,2,4-tri-O-acetyl-3,6-dideoxy-3,6-difluoro-β-D-glucopyranose
  参考文献：
  名称：

  一系列脱氧和脱氧氟-α-d-“吡喃葡萄糖基”磷酸酯的合成和水解

  摘要：

  摘要描述了三种脱氧-α-d-“吡喃葡萄糖基”磷酸酯和一系列双脱氧单氟-和双脱氧二氟-α-d-吡喃葡萄糖基磷酸酯的合成。测定其酸催化水解的速率常数。已显示糖环中的脱氧可将水解速率提高至先前对一系列苯基脱氧d-“吡喃葡萄糖苷”进行酸催化水解所见的程度[Mega and Matsushima，J. Biochem。东京，94（1983）1637]。这表明这两个反应的过渡态基本相同。通过确定一系列脱氧和脱氧氟取代的6-脱氧-6-氟-α-d-葡萄糖基吡喃糖基磷酸酯的水解速率，可证明对糖环的取代基作用具有可预测的加性，并且本质上主要是电子的，

  DOI：

  10.1016/0008-6215(89)80055-2
• 作为产物：
  描述：

  1,2:5,6-di-O-isopropylidene-3-O-trifluoromethanesulfonyl-α-D-allofuranose 在 硫酸 、 cesium fluoride 作用下， 以 甲醇 、 水 、 叔丁醇 为溶剂， 反应 44.0h， 生成 3-deoxy-3-fluoro-1,2-O-isopropylidene-α-D-glucofuranose
  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

• Synthesis of a 2,3-dideoxy-2,3-difluorofuranose with the d-lyxo configuration. An intramolecular rearrangement of methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-d-lyxofuranoside observed during the attempted synthesis of 1-(2,3-dideoxy-2,3-difluoro-β-d-lyxofuranosyl)thymine
  作者：Lak S. Jeong、Benjamin B. Lim、Victor E. Marquez

  DOI：10.1016/0008-6215(94)84007-5

  日期：1994.9

  diethylaminosulfur trifluoride (DAST). An attempt to use 8 in the synthesis of the all-cis nucleoside, 1-(2,3-dideoxy-2,3-difluoro-beta-D-lyxofuranosyl)thymine, failed to give the desired product, providing instead 1-(3-deoxy-3-fluoro-2-O-methyl-beta-D-xylofuranosyl)thymine (11), the structure of which was confirmed by an independent synthesis. Formation of the rearranged product occurred with the concurrent

  由1合成了一种新的糖，甲基5-O-苯甲酰基-2,3-二脱氧-2,3-二氟-D-呋喃呋喃糖苷（8），其特征是在四氢呋喃环平面上方的相邻碳位置上具有氟取代基。 ，2：7个步骤中的5，6-二-O-异丙基吡啶-α-D-呋喃糖，总产率为22％。在合成过程中，引入第二个氟原子所需的条件要比通常与二乙基氨基三氟化硫（DAST）一起使用的条件更为严格。在全顺式核苷1-（2,3-dideoxy-2,3-difluoro-beta-D-lyxofuranosyl）thymine的合成中尝试使用8的尝试未能获得所需的产物，而是提供了1-（ 3-脱氧-3-氟-2-O-甲基-β-D-呋喃呋喃糖基）胸腺嘧啶（11），其结构通过独立合成得到证实。重排产物的形成与氟的同时损失和甲氧基的保留同时发生，甲氧基从异头异构体转移到2'-位置。本工作突出了这种新型双脱氧二氟糖前体的反应性。
• Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents
  作者：Evangelia Tsoukala、Niki Tzioumaki、Stella Manta、Alexandra Riga、Jan Balzarini、Dimitri Komiotis

  DOI：10.1016/j.bioorg.2010.08.001

  日期：2010.12

  were prepared via two facile synthetic routes. Their precursors, 3-fluoro-6-thio-glucopyranosyl nucleosides 5a-e, were obtained by the sequence of deacetylation of 3-deoxy-3-fluoro-β-d-glucopyranosyl nucleosides 2a-e, selective tosylation of the primary OH of 3 and finally treatment with potassium thioacetate. The desired thiolpyridine protected analogs 7a-c,f,g were obtained by the sequence of deacetylation

  3-脱氧-3-氟-6-小号- （2-小号吡啶基）-6-硫代β - d吡喃葡萄糖基的核苷类似物7制备通过2条容易合成路线。它们的前体，3-氟-6-硫代-吡喃葡萄糖基核苷5a - e，是通过 3-脱氧-3-氟-β - d-吡喃葡萄糖基核苷2a - e的脱乙酰化序列，选择性甲苯磺酰化的初级 OH 获得的。3最后用硫代乙酸钾处理。所需的硫醇吡啶保护的类似物7a - c，˚F，克由脱乙酰的序列获得5A - Ç随后thiopyridinylation和/或与新合成的全乙酰-6-相应杂环碱缩合小号- （2-小号吡啶基）糖前体13，其中获得通过从糖基供体12的新合成路线。化合物6和7均不显示抗病毒活性，但5-氟尿嘧啶衍生物7c，尤其是尿嘧啶衍生物7b 被赋予了对多种鼠类和人肿瘤细胞培养物的有趣且选择性的细胞抑制作用。
• 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。
• An efficient synthesis of 3-fluoro-5-thio-xylofuranosyl nucleosides of thymine, uracil, and 5-fluorouracil as potential antitumor or/and antiviral agents
  作者：Evangelia Tsoukala、George Agelis、Jan Dolinšek、Tanja Botić、Avrelija Cencič、Dimitri Komiotis

  DOI：10.1016/j.bmc.2007.02.031

  日期：2007.5

  5-thio-D-xylofuranose (7). Condensation of 7 with silylated thymine, uracil, and 5-fluorouracil afforded nucleosides 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio-beta-D-xylofuranosyl) thymine (8), 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio-beta-D-xylofuranosyl) uracil (9), and 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio-beta-D-xylofuranosyl) 5-fluorouracil (10). Compounds 8, 9, and 10 are biologically active against

  1,2：5,6-二-O-异亚丙基-α-D-葡萄糖基呋喃糖通过轻度氧化，还原，氟化，高碘酸盐氧化，硼氢化物还原和磺酰化的顺序得到3-脱氧-3-氟-1,2 -O-异亚丙基-5-Op-甲苯磺酰基-α-D-木呋喃糖（5）。将甲苯磺酸酯5转化为硫代乙酸酯衍生物6，其在乙酰分解后得到1,2-二-O-乙酰基-5-S-乙酰基-3-脱氧-3-氟-5-硫代-D-木呋喃糖（7）。将7与甲硅烷基胸腺嘧啶，尿嘧啶和5-氟尿嘧啶缩合可得到核苷1-（5-S-乙酰-3-脱氧-3-氟-5-硫代-β-D-呋喃呋喃糖基）胸腺嘧啶（8），1-（ 5-S-乙酰基-3-脱氧-3-氟-5-硫代-β-D-呋喃呋喃糖基）尿嘧啶（9）和1-（5-S-乙酰基-3-脱氧-3-氟-5-硫代） -β-D-木呋喃糖基）5-氟尿嘧啶（10）。化合物8、9和10对轮状病毒感染和肿瘤细胞的生长具有生物活性。