2,4,6-tri-O-acetyl-1,5-anhydro-3-deoxy-3-fluoro-D-glucitol | 1337926-42-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,4,6-tri-O-acetyl-1,5-anhydro-3-deoxy-3-fluoro-D-glucitol
• 英文别名: 1,5-anhydro-3-deoxy-3-fluoro-2,4,6-triacetyl-D-glucitol；[(2R,3R,4R,5S)-3,5-diacetyloxy-4-fluorooxan-2-yl]methyl acetate
• CAS: 1337926-42-7
• 化学式: C₁₂H₁₇FO₇
• 分子量: 292.261
• InChiKey: CXWWPVPXORAZHP-IRCOFANPSA-N

物化性质

• 沸点：
  354.2±42.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,4,6-tri-O-acetyl-1,5-anhydro-3-deoxy-3-fluoro-D-glucitol 在 吡啶 、 N-甲基咪唑 、 四氮唑 、 20% palladium hydroxide on charcoal 、 氢气 、 potassium carbonate 、 对甲苯磺酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 1,5-anhydro-4-O-(cyanoethoxydiisopropylaminophosphinyl)-2,3-dideoxy-6-O-(4,4'-dimethoxytrityl)-3-fluoro-2-(thymin-1-yl)-D-mannitol
  参考文献：
  名称：

  Synthesis, Improved Antisense Activity and Structural Rationale for the Divergent RNA Affinities of 3′-Fluoro Hexitol Nucleic Acid (FHNA and Ara-FHNA) Modified Oligonucleotides

  摘要：

  The synthesis, biophysical, structural, and biological properties of both isomers of 3'-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides are reported. Synthesis of the FHNA and Ara-FHNA thymine phosphoramidites was efficiently accomplished starting from known sugar precursors. Optimal RNA affinities were observed with a 3'-fluorine atom and nucleobase in a trans-diaxial orientation. The Ara-FHNA analog with an equatorial fluorine was found to be destabilizing. However, the magnitude of destabilization was sequence-dependent. Thus, the loss of stability is sharply reduced when Ara-FHNA residues were inserted at pyrimidine-purine (Py-Pu) steps compared to placement within a stretch of pyrimidines (Py-Py). Crystal structures of A-type DNA duplexes modified with either monomer provide a rationalization for the opposing stability effects and point to a steric origin of the destabilization caused by the Ara-FHNA analog. The sequence dependent effect can be explained by the formation of an internucleotide C-F center dot center dot center dot H-C pseudo hydrogen bond between F3' of Ara-FHNA and C8-H of the nucleobase from the 3'-adjacent adenosine that is absent at Py-Py steps. In animal experiments, FHNA-modified antisense oligonudeotides formulated in saline showed a potent downregulation of gene expression in liver tissue without producing hepatotoxicity. Our data establish FHNA as a useful modification for antisense therapeutics and also confirm the stabilizing influence of F(Py)center dot center dot center dot H-C(Pu) pseudo hydrogen bonds in nucleic acid structures.

  DOI：

  10.1021/ja207086x
• 作为产物：
  描述：

  3-deoxy-3-fluoro-1,2,4,6-tetra-O-acetyl-D-glucopyranose 在 三乙基硼 、 三(三甲基硅基)硅烷 、 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 19.0h， 生成 2,4,6-tri-O-acetyl-1,5-anhydro-3-deoxy-3-fluoro-D-glucitol
  参考文献：
  名称：

  1,5-脱水-d-果糖衍生物的合成及其炎性体抑制剂的评价

  摘要：

  几个1,5-脱水-的合成d -fructose（1,5- AF）衍生物的炎性进行评价抑制活性。近来，据报道1，5-AF抑制炎症小体，尽管活性低。我们着眼于2-酮形式的1,5-AF的水合，并推测这种水合是低活性的原因。因此，我们合成了一些1,5-AF衍生物，这些衍生物将无法形成二聚体构象，并且有望对炎症小体具有较高的活性，然后通过使用小鼠骨髓-核糖核酸评估它们对NLRP3炎症小体的抑制活性。衍生的巨噬细胞和人类THP-1细胞。结果，某些合成的2-酮形式的化合物对NLRP3炎性小体的抑制活性比1,5-AF高得多。

  DOI：

  10.1016/j.bmc.2017.11.041

文献信息

• [EN] AMINOGLYCOSIDES AND USES THEREOF<br/>[FR] AMINOGLYCOSIDES ET LEURS UTILISATIONS
  申请人：ACHAOGEN INC

  公开号：WO2019046126A1

  公开（公告）日：2019-03-07

  Provided herein are aminoglycoside compounds, such as compounds of formula (I), (II), (III), (IV), (IVa), (V), (VI), (VIIa), or (VIIb) or pharmaceutically acceptable salts, solvates, stereoisomers, or tautomers of any of the foregoing, useful as therapeutic or prophylactic agents. Also provided herein are methods for their preparation. The compounds may be useful in treating a bacterial infection in a subject, for example a Gram-negative bacterial infection.

  本文提供了氨基糖苷化合物，例如式(I)、(II)、(III)、(IV)、(IVa)、(V)、(VI)、(VIIa)或(VIIb)的化合物，或者上述任何一个的药用盐、溶剂化合物、立体异构体或互变异构体，可用作治疗或预防剂。本文还提供了它们的制备方法。这些化合物可能在治疗受试者的细菌感染方面有用，例如革兰氏阴性细菌感染。
• [EN] MODULAR SYNTHESIS OF AMINOGLYCOSIDES<br/>[FR] SYNTHÈSE MODULAIRE D'AMINOGLYCOSIDES
  申请人：ACHAOGEN INC

  公开号：WO2019194858A1

  公开（公告）日：2019-10-10

  The present disclosure relates to novel methods for preparing antibacterial aminoglycoside compounds and the compounds used in such preparations.

  本公开涉及制备抗菌氨基糖苷化合物的新方法以及用于这种制备中的化合物。
• MODULAR SYNTHESIS OF AMINOGLYCOSIDES
  申请人：REVAGENIX, INC.

  公开号：US20220411456A1

  公开（公告）日：2022-12-29

  The present disclosure relates to novel methods for preparing antibacterial aminoglycoside compounds and the compounds used in such preparations.