methyl 2,3-di-O-tetradecyl-α-D-glucopyranoside | 150126-34-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2,3-di-O-tetradecyl-α-D-glucopyranoside
• CAS: 150126-34-4
• 化学式: C₃₅H₇₀O₆
• 分子量: 586.937
• InChiKey: XHKQWCLDPUFVIT-KJQSSVQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.88
• 重原子数：
  41.0
• 可旋转键数：
  30.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  77.38
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 2,3-di-O-tetradecyl-α-D-glucopyranoside 在 咪唑 、 碘 、 caesium carbonate 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 27.0h， 生成 methyl 6-(2-aminoethylthio)-2,3-di-O-tetradecyl-α-D-glucopyranoside hydrochloride
  参考文献：
  名称：

  Trehalose- and Glucose-Derived Glycoamphiphiles: Small-Molecule and Nanoparticle Toll-Like Receptor 4 (TLR4) Modulators

  摘要：

  An increasing number of pathologies have been linked to Toll-like receptor 4 (TLR4) activation and signaling, therefore new hit and lead compounds targeting this receptor activation process are urgently needed. We report on the synthesis and biological properties of glycolipids based on glucose and trehalose scaffolds which potently inhibit TLR4 activation and signaling in vitro and in vivo. Structure-activity relationship studies on these compounds indicate that the presence of fatty ester chains in the molecule is a primary prerequisite for biological activity and point to facial amphiphilicity as a preferred architecture for TLR4 antagonism. The cationic glycolipids here presented can be considered as new lead compounds for the development of drugs targeting TLR4 activation and signaling in infectious, inflammatory, and autoimmune diseases. Interestingly, the biological activity of the best drug candidate was retained after adsorption at the surface of colloidal gold nanoparticles, broadening the options for clinical development.

  DOI：

  10.1021/jm501182w
• 作为产物：
  描述：

  溴代十四烷 在 aluminum (III) chloride 、 sodium hydride 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.0h， 生成 methyl 2,3-di-O-tetradecyl-α-D-glucopyranoside
  参考文献：
  名称：

  Trehalose- and Glucose-Derived Glycoamphiphiles: Small-Molecule and Nanoparticle Toll-Like Receptor 4 (TLR4) Modulators

  摘要：

  An increasing number of pathologies have been linked to Toll-like receptor 4 (TLR4) activation and signaling, therefore new hit and lead compounds targeting this receptor activation process are urgently needed. We report on the synthesis and biological properties of glycolipids based on glucose and trehalose scaffolds which potently inhibit TLR4 activation and signaling in vitro and in vivo. Structure-activity relationship studies on these compounds indicate that the presence of fatty ester chains in the molecule is a primary prerequisite for biological activity and point to facial amphiphilicity as a preferred architecture for TLR4 antagonism. The cationic glycolipids here presented can be considered as new lead compounds for the development of drugs targeting TLR4 activation and signaling in infectious, inflammatory, and autoimmune diseases. Interestingly, the biological activity of the best drug candidate was retained after adsorption at the surface of colloidal gold nanoparticles, broadening the options for clinical development.

  DOI：

  10.1021/jm501182w

文献信息

• Synthesis of a 1α,4'-Di-O-allylated, 2,3,2',3'-Tetra-O-tetradecylated Lipid A Mimic and Its 4-O-(4-Methoxybenzyl) Precursor
  作者：Marek Baráth、Mária Petrušová、Ján Hirsch、Ladislav Petruš

  DOI：10.1135/cccc20061532

  日期：——

  Compound18mimicking lipid A, containing D-glucose instead of D-glucosamine moieties in its gentiobiose skeleton,O-tetradecyl groups at the C-2, C-3, C-2' and C-3' instead of the ester- and amide-linked fatty acids, andO-allyl groups at the C-1α and C-4' replacing the phosphate groups, was synthesized by the Schmidt trichloroacetamidate method in a combined 8% yield of 13 steps. Allyl 4,6-O-(4-methoxybenzylidene)-α-D-glucopyranoside (1) and methyl 4,6-O-benzylidene-α-D-glucopyranoside (4) were starting materials for preparation of the respectiveO-alkylated andO-allylated glycosyl donor and sugar nucleophile. While boron trifluoride etherate in dichloromethane catalysed a highly preferential formation of the required β-(1→6)-glycosidic bond, α-linked lipidodisaccharide was a major product when trimethylsilyl trifluoromethanesulfonate was used as a catalyst, in both cases independently of the anomeric configuration of the starting imidate. Prolonged treatment with acid catalysts in the coupling step was exploited also for a one-pot removal of the intermediate 4-O-(4-methoxybenzyl) protection of the target mimic18of lipid A.

  合成了一种类脂A的化合物18，其龙胆二糖骨架中的D-葡萄糖胺基团被替换为D-葡萄糖基团，C-2、C-3、C-2'和C-3'位置上的酯和酰胺连接的脂肪酸被替换为O-十四烷基，C-1α和C-4'位置上的磷酸基团被替换为O-丙烯基，该化合物通过Schmidt三氯乙酰胺法合成，共13步，总收率为8％。丙烯基4,6-O-(4-甲氧基苯甲醛基)-α-D-葡萄糖苷(1)和甲基4,6-O-苯甲醛基-α-D-葡萄糖苷(4)是制备相应的O-烷基化和O-丙烯基化糖基供体和糖核苷的起始物质。在二氯甲烷中，三氟化硼醚催化高度优先形成所需的β-(1→6)-糖苷键，当三甲基硅基三氟甲磺酸盐用作催化剂时，α-连接的脂肪二糖是主要产物，在两种情况下，不管起始亚胺的异构构型如何。在偶联步骤中，长时间使用酸催化剂还可用于一锅法去除目标类脂A的中间体4-O-(4-甲氧基苯甲醇)保护基。