2-deoxy-6-O-[2-deoxy-4-O-phosphono-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-β-D-glucopyranosyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-D-glucopyranose

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-deoxy-6-O-[2-deoxy-4-O-phosphono-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-β-D-glucopyranosyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-D-glucopyranose
• 英文别名: 2-deoxy-6-O-{2-deoxy-4-O-phosphono-2-[(R)-3-tetradecanoyloxytetradecanamido]-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-β-D-glucopyranosyl}-2-[(R)-3-tetradecanoyloxytetradecanamido]-D-glucopyranose；[(2R,3S,4R,5R,6R)-2-(hydroxymethyl)-3-phosphonooxy-5-[[(3R)-3-tetradecanoyloxytetradecanoyl]amino]-6-[[(2R,3S,4R,5R)-3,4,6-trihydroxy-5-[[(3R)-3-tetradecanoyloxytetradecanoyl]amino]oxan-2-yl]methoxy]oxan-4-yl] (3R)-3-tetradecanoyloxytetradecanoate
• 化学式: C₉₆H₁₈₁N₂O₂₁P
• 分子量: 1730.47
• InChiKey: GQJJDLWSTDOFJY-GNXMWRSVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  29.3
• 重原子数：
  120
• 可旋转键数：
  88
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  339
• 氢给体数：
  8
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  benzyl 2-deoxy-6-O-[2-deoxy-4-O-diphenylphosphono-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-β-D-glucopyranosyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-β-D-glucopyranoside 在 钯 、 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 20.0 ℃ 、482.63 kPa 条件下， 反应 42.0h， 以0.61 g的产率得到2-deoxy-6-O-[2-deoxy-4-O-phosphono-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-β-D-glucopyranosyl]-2-[(R)-3-tetradecanoyloxytetradecanoylamino]-D-glucopyranose
  参考文献：
  名称：

  3-O-Desacyl Monophosphoryl Lipid A Derivatives:  Synthesis and Immunostimulant Activities

  摘要：

  The synthesis of a series of novel analogues of lipid A, the active principle of lipopolysaccharide, is reported. In these compounds, the 1-O-phosphono and (R)-3-hydroxytetradecanoyl moieties of native Salmonella minnesota R595 lipid A have been replaced with hydrogen and the length of the normal fatty acyl residues has been systematically varied. Normal fatty acid chain length in the 3-O-desacyl monophosphoryl lipid A (MLS) series is shown to be a critical determinant of iNOS gene expression in activated mouse macrophages and the induction of proinflammatory cytokines in human peripheral monocytes. Examination of pyrogenicity in rabbits and lethal toxicity in D-galactosamine-treated mice shows that toxic effects in the MLA series can be ameliorated by modifying fatty acid chain length. When used as an adjuvant for tetanus toroid vaccines, certain MLA derivatives enhance the production of tetanus toroid-specific antibodies in mice.

  DOI：

  10.1021/jm990222b

文献信息

• Monophosphoryl lipid A analogues with varying 3-O-substitution: synthesis and potent adjuvant activity
  作者：Zi-Hua Jiang、Wladyslaw A. Budzynski、Dongxu Qiu、Damayanthi Yalamati、R. Rao Koganty

  DOI：10.1016/j.carres.2007.01.012

  日期：2007.5

  Salmonella minnesota R595 (R595 lipid A). The substituent at the 3-O-position of the reducing sugar does not have much effect on the adjuvant activity of monophosphoryl lipid A analogues. The preliminary lethal toxicity study indicates that the 3-O-acylated hepta-acyl monophosphoryl lipid A may not be more toxic than its 3-O-deacylated hexa-acyl analogue.

  结构确定的免疫刺激佐剂在新一代疫苗的开发中起重要作用。这里描述了在还原糖的3-O-位具有不同取代的三种单磷酰基脂质A类似物（1-3）的合成及其有效的免疫刺激佐剂活性。合成涉及糖基化受体苄基3，4-二-O-苄基-2-脱氧-2-[（R）-3-十四烷酰氧基四癸酰胺基]-β-D-葡萄糖吡喃糖苷（16）和苄基3-O-的制备。烯丙基-4-O-苄基-2-脱氧-2-[（R）-3-十四烷酰氧基四癸酰胺基]-β-D-glu复制糖苷（17）。供体4,6-二-O-亚苄基-2-脱氧-2-（2'，2'，2'-三氯乙氧基羰基氨基）-α-d-gl核糖基三氯乙酰亚氨酸酯（21）与受体16和17之间的糖基化反应提供所需的beta-（1-> 6）-连接的二糖22和23。4，6-二-O-亚苄基的选择性还原性开环，在4'-羟基上安装磷酸基团，以及最终的整体脱苄基作用产生了设计的单磷酰基脂质A类似物1-3。在全合成脂质体疫苗系统的离