phenyl 3-O-acetyl-2-azido-4-O-benzyl-2-deoxy-1-thio-α-D-glucopyranoside | 173465-74-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: phenyl 3-O-acetyl-2-azido-4-O-benzyl-2-deoxy-1-thio-α-D-glucopyranoside
• 英文别名: [(2R,3S,4R,5R,6R)-5-azido-2-(hydroxymethyl)-3-phenylmethoxy-6-phenylsulfanyloxan-4-yl] acetate
• CAS: 173465-74-2
• 化学式: C₂₁H₂₃N₃O₅S
• 分子量: 429.497
• InChiKey: WUFWKPNBJMHBGV-PFAUGDHASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  phenyl 3-O-acetyl-2-azido-4-O-benzyl-2-deoxy-1-thio-α-D-glucopyranoside 在 MS 4 Angstroem 、 silver trifluoromethanesulfonate 、 potassium carbonate 、 乙二胺 作用下， 以 二氯甲烷 、 正丁醇 为溶剂， 反应 22.0h， 生成 phenyl 6-O-(2-amino-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-2-azido-4-O-benzyl-2-deoxy-1-thio-α-D-glucopyranoside
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Rhizobium sin-1 Lipid A Derivatives

  摘要：

  A highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin-1 has been developed. The approach employed the advanced intermediate 3-O-acetyl-6-O-(3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyrano-syl)-2-azido-4-O-benzyl-2-deoxy-1 -thio-alpha-D-glucopyranoside (5), which is protected in such a way that the anomeric center, the C-2 and C-2' amino groups, and the C-3 and C-3' hydroxyls can be selectively functionalized. The synthetic strategy was used for the preparation of 2-deoxy-6-O-12-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]- alpha-D-glucopyranose (11) and 2-deoxy-6-O-{2-deoxy-3-O[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-D-glucono-1,5-lactone (13), which contain an unusual octacosanoic acid moiety and differ in the oxidation state of the anomeric center. The results of biological studies indicate that 11 and 13 lack the proinflammatory effects of Escherichia coli lipopolysaccharicles (LPS). Furthermore, 13 emulated the ability of heterogeneous R. sin-1 LPS to antagonize enteric LPS, providing evidence for the critical role of the gluconolactone moiety of R. sin-1 LPS in mediating this antagonistic effect. Compound 13 is the first example of a lipid A derivative that is devoid of phosphate but possesses antagonistic properties, making it an attractive lead compound for development of a drug to use in the treatment of Gram-negative septicemia.

  DOI：

  10.1021/ja029316s
• 作为产物：
  描述：

  3-O-acetyl-2-azido-4-O-benzyl-1,6-anhydroglucose 在 三氟乙酸 、 zinc(II) iodide 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 16.17h， 生成 phenyl 3-O-acetyl-2-azido-4-O-benzyl-2-deoxy-1-thio-α-D-glucopyranoside
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Rhizobium sin-1 Lipid A Derivatives

  摘要：

  A highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin-1 has been developed. The approach employed the advanced intermediate 3-O-acetyl-6-O-(3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyrano-syl)-2-azido-4-O-benzyl-2-deoxy-1 -thio-alpha-D-glucopyranoside (5), which is protected in such a way that the anomeric center, the C-2 and C-2' amino groups, and the C-3 and C-3' hydroxyls can be selectively functionalized. The synthetic strategy was used for the preparation of 2-deoxy-6-O-12-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]- alpha-D-glucopyranose (11) and 2-deoxy-6-O-{2-deoxy-3-O[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-D-glucopyranosyl}-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-D-glucono-1,5-lactone (13), which contain an unusual octacosanoic acid moiety and differ in the oxidation state of the anomeric center. The results of biological studies indicate that 11 and 13 lack the proinflammatory effects of Escherichia coli lipopolysaccharicles (LPS). Furthermore, 13 emulated the ability of heterogeneous R. sin-1 LPS to antagonize enteric LPS, providing evidence for the critical role of the gluconolactone moiety of R. sin-1 LPS in mediating this antagonistic effect. Compound 13 is the first example of a lipid A derivative that is devoid of phosphate but possesses antagonistic properties, making it an attractive lead compound for development of a drug to use in the treatment of Gram-negative septicemia.

  DOI：

  10.1021/ja029316s

文献信息

• The influence of the long chain fatty acid on the antagonistic activities of Rhizobium sin-1 lipid A
  作者：Yanghui Zhang、Margreet A. Wolfert、Geert-Jan Boons

  DOI：10.1016/j.bmc.2007.05.012

  日期：2007.7

  27-hydroxyoctacosanoic acid for antagonistic properties, a highly convergent strategy for the synthesis of several derivatives of the lipid A of R. sin-1 has been developed. Compound 1 is a natural R. sin-1 lipid A having a 27-hydroxyoctacosanoic acid at C-2', compound 2 contains an octacosanoic acid moiety at this position, and compound 3 is modified by a short chain tetradecanoic acid. Cellular activation

  来自固氮细菌根瘤菌 sin-1 的脂质 A 在结构上是不寻常的，因为缺乏磷酸盐并且存在 2-氨基葡萄糖酸内酯和极长链脂肪酸 27-羟基二十八烷酸 (27OHC28:0) 部分。这种结构上不寻常的脂质 A 可以拮抗大肠​​杆菌 LPS 诱导的人单核细胞产生 TNF-α。为了确定不寻常的长链 27-羟基二十二烷酸与拮抗特性的相关性，开发了一种高度收敛的策略来合成 R. sin-1 的脂质 A 的几种衍生物。化合物1是在C-2'处具有27-羟基二十二烷酸的天然R.sin-1脂质A，化合物2在该位置含有二十八烷酸部分，并且化合物3被短链十四烷酸修饰。对人类单核细胞系的细胞活化研究表明，二十八烷酸对于最佳拮抗特性非常重要。然而，天然 27-羟基二十八烷酸部分的羟基并不能解释抑制活性。由此产生的结构-活性关系对于设计治疗感染性休克的化合物非常重要。
• Conformationally Armed 3,6-Tethered Glycosyl Donors: Synthesis, Conformation, Reactivity, and Selectivity
  作者：Mads Heuckendorff、Christian Marcus Pedersen、Mikael Bols

  DOI：10.1021/jo4012464

  日期：2013.7.19

  The reactivity and selectivity of 3,6-tethered glycosyl donors have been studied using acceptors with different steric and electronic characteristics. Eight (four anomeric pairs) 3,6-bridged-glycosyl donors were synthesized in high yields from their common parent sugars. The glycosylation properties were tested using at least three different acceptors and several promoter systems. Thiophenyl 2,4-di-O-benzyl-3,6-O-(di-tert-butylsilylene)-alpha-D-glucopyranoside gave alpha/beta mixtures with standard NIS/TfOH mediated activation, whereas the corresponding fluoride was found to be highly beta-selective, when using SnCl2/AgE(C6F5)(4) as the promoter system. Mannosyl donors were highly alpha-selective despite the altered conformation. Galactosylations using NIS/TfOH were generally alpha-selective, but more beta-selective using the galactosyl fluoride and depending on the acceptor used. Thiophenyl 2-azido-2-deoxy-4-O-benzyl-3,6-O-(di-tert-butylsilylene)-alpha-D-glucopyranoside was found to be alpha-selective. The reactivity of the donors was investigated using competition experiments, and some but not all were found to be highly reactive. Generally it was found that the alpha-thioglycosides were significantly more reactive than the beta; this difference in reactivity was not found for 3,6-anhydro-, armed-(benzylated), or the classic super armed (silylated) donors. A mechanism supporting the unusual observations has been suggested.