benzyl N-trichloroethoxycarbonyl-O-[6-O-tert-butyldimethylsilyl-2-N-trichloroethoxycarbonyl-β-D-glucopyranosyl]-L-serinate | 640291-23-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: benzyl N-trichloroethoxycarbonyl-O-[6-O-tert-butyldimethylsilyl-2-N-trichloroethoxycarbonyl-β-D-glucopyranosyl]-L-serinate
• 英文别名: benzyl (2S)-3-[(2R,3R,4R,5S,6R)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-4,5-dihydroxy-3-(2,2,2-trichloroethoxycarbonylamino)oxan-2-yl]oxy-2-(2,2,2-trichloroethoxycarbonylamino)propanoate
• CAS: 640291-23-2
• 化学式: C₂₈H₄₀Cl₆N₂O₁₁Si
• 分子量: 821.436
• InChiKey: HDGUMPRIPBUCBK-CFPLAWGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  171
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  benzyl N-trichloroethoxycarbonyl-O-[6-O-tert-butyldimethylsilyl-2-N-trichloroethoxycarbonyl-β-D-glucopyranosyl]-L-serinate 、 (R)-3-decanoyloxytetradecanoic acid 在 4-二甲氨基吡啶 、 二甲基氨基丙基乙基碳酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以85%的产率得到[(2R,3S,4R,5R,6R)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-hydroxy-6-[(2S)-3-oxo-3-phenylmethoxy-2-(2,2,2-trichloroethoxycarbonylamino)propoxy]-5-(2,2,2-trichloroethoxycarbonylamino)oxan-4-yl] (3R)-3-decanoyloxytetradecanoate
  参考文献：
  名称：

  The ‘Ethereal’ nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics

  摘要：

  To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonist activity in both in vitro and in vivo models. Like CRX-527, the secondary ether lipid 4 showed potent agonist activity in both murine and human models. Ether lipid 5, on the other hand, showed potent TLR4 antagonist activity similar to CRX-526 in human cell assays, but did not display any antagonist activity in murine models and, in fact, was weakly agonistic. Glycolipids 2, 4, and 5 were synthesized via a new highly convergent method utilizing a common advanced intermediate strategy. A new method for preparing (R)-3-alkyloxytetradecanoic acids, a key component of ether lipids 4 and 5, is also described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.060
• 作为产物：
  描述：

  2-deoxy-2-(2,2,2-trichloroethoxycarbonylamino)-D-glucopyranose 在 吡啶 、 ammonium hydroxide 、 三氟化硼乙醚 、 四丁基溴化铵 、 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 99.0h， 生成 benzyl N-trichloroethoxycarbonyl-O-[6-O-tert-butyldimethylsilyl-2-N-trichloroethoxycarbonyl-β-D-glucopyranosyl]-L-serinate
  参考文献：
  名称：

  自缀合脂质A类似物和合成长肽的自佐剂癌症疫苗。

  摘要：

  抗原肽与免疫刺激剂共价结合的自佐剂疫苗已被证明是用于免疫疗法的有前途的工具。合成的Toll样受体（TLR）配体是与肽或蛋白质共价连接的理想佐剂。在此，我们在新型偶联物-疫苗形式的产生中，引入了偶联准备就绪的TLR4配体CRX-527，一种有效的强大脂质A类似物。已经开发了用于结合准备的配体的合成以及其与肽抗原的连接的有效化学。探索了不同的接头系统和模型肽的连接模式，并在体外对缀合物的评估显示它们是强大的免疫激活剂，比单独的成分更有效。将CRX-527配体安装在模型肽抗原的N末端可提供一种疫苗形式，该疫苗形式被证明可有效激活树突状细胞，促进抗原呈递以及启动特异性CD8 + T细胞介导的抗原杀伤体内加载的靶细胞。因此，合成的TLR4配体在增强缀合疫苗平台用于癌症疫苗接种中显示出巨大的希望。

  DOI：

  10.1021/acs.jmedchem.0c00851

文献信息

• Self-Adjuvanting Cancer Vaccines from Conjugation-Ready Lipid A Analogues and Synthetic Long Peptides
  作者：Niels R. M. Reintjens、Elena Tondini、Ana R. de Jong、Nico J. Meeuwenoord、Fabrizio Chiodo、Evert Peterse、Herman S. Overkleeft、Dmitri V. Filippov、Gijsbert A. van der Marel、Ferry Ossendorp、Jeroen D. C. Codée

  DOI：10.1021/acs.jmedchem.0c00851

  日期：2020.10.22

  conjugates showed them to be powerful immune-activating agents, significantly more effective than the separate components. Mounting the CRX-527 ligand at the N-terminus of the model peptide antigen delivered a vaccine modality that proved to be potent in activation of dendritic cells, in facilitating antigen presentation, and in initiating specific CD8+ T-cell-mediated killing of antigen-loaded target

  抗原肽与免疫刺激剂共价结合的自佐剂疫苗已被证明是用于免疫疗法的有前途的工具。合成的Toll样受体（TLR）配体是与肽或蛋白质共价连接的理想佐剂。在此，我们在新型偶联物-疫苗形式的产生中，引入了偶联准备就绪的TLR4配体CRX-527，一种有效的强大脂质A类似物。已经开发了用于结合准备的配体的合成以及其与肽抗原的连接的有效化学。探索了不同的接头系统和模型肽的连接模式，并在体外对缀合物的评估显示它们是强大的免疫激活剂，比单独的成分更有效。将CRX-527配体安装在模型肽抗原的N末端可提供一种疫苗形式，该疫苗形式被证明可有效激活树突状细胞，促进抗原呈递以及启动特异性CD8 + T细胞介导的抗原杀伤体内加载的靶细胞。因此，合成的TLR4配体在增强缀合疫苗平台用于癌症疫苗接种中显示出巨大的希望。
• The ‘Ethereal’ nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics
  作者：Hélène G. Bazin、Tim J. Murray、William S. Bowen、Afsaneh Mozaffarian、Steven P. Fling、Laura S. Bess、Mark T. Livesay、Jeffrey S. Arnold、Craig L. Johnson、Kendal T. Ryter、Christopher W. Cluff、Jay T. Evans、David A. Johnson

  DOI：10.1016/j.bmcl.2008.09.060

  日期：2008.10

  To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonist activity in both in vitro and in vivo models. Like CRX-527, the secondary ether lipid 4 showed potent agonist activity in both murine and human models. Ether lipid 5, on the other hand, showed potent TLR4 antagonist activity similar to CRX-526 in human cell assays, but did not display any antagonist activity in murine models and, in fact, was weakly agonistic. Glycolipids 2, 4, and 5 were synthesized via a new highly convergent method utilizing a common advanced intermediate strategy. A new method for preparing (R)-3-alkyloxytetradecanoic acids, a key component of ether lipids 4 and 5, is also described. (C) 2008 Elsevier Ltd. All rights reserved.