1-O-[2-[S-[(2R)-2,3-bis(palmitoyloxy)propyl]-N-(tert-butoxycarbonyl)-(R)-cysteinyl-amino]ethyl]-2,3,5,6-tetra-O-benzyl-α-D-galactofuranose | 1375100-22-3

• 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: 1-O-[2-[S-[(2R)-2,3-bis(palmitoyloxy)propyl]-N-(tert-butoxycarbonyl)-(R)-cysteinyl-amino]ethyl]-2,3,5,6-tetra-O-benzyl-α-D-galactofuranose
• 英文别名: [(2R)-3-[(2R)-3-[2-[(2S,3R,4S,5S)-5-[(1R)-1,2-bis(phenylmethoxy)ethyl]-3,4-bis(phenylmethoxy)oxolan-2-yl]oxyethylamino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]sulfanyl-2-hexadecanoyloxypropyl] hexadecanoate
• CAS: 1375100-22-3
• 化学式: C₇₉H₁₂₀N₂O₁₃S
• 分子量: 1337.89
• InChiKey: KHLHIRDUGQRTTQ-NTNNAFBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  20.8
• 重原子数：
  95
• 可旋转键数：
  59
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  201
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  1-O-[2-[S-[(2R)-2,3-bis(palmitoyloxy)propyl]-N-(tert-butoxycarbonyl)-(R)-cysteinyl-amino]ethyl]-2,3,5,6-tetra-O-benzyl-α-D-galactofuranose 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 72.0h， 以40%的产率得到
  参考文献：
  名称：

  Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: Synthesis and biological properties

  摘要：

  A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-alpha-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an alpha-Galactosylpyranose or an alpha-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (alpha/beta ratio > 9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.039
• 作为产物：
  描述：

  、 N-α-Boc-S-[(2R)-2,3-bis(palmitoyloxy)propyl]-L-cysteine 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以69%的产率得到1-O-[2-[S-[(2R)-2,3-bis(palmitoyloxy)propyl]-N-(tert-butoxycarbonyl)-(R)-cysteinyl-amino]ethyl]-2,3,5,6-tetra-O-benzyl-α-D-galactofuranose
  参考文献：
  名称：

  Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: Synthesis and biological properties

  摘要：

  A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-alpha-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an alpha-Galactosylpyranose or an alpha-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (alpha/beta ratio > 9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.039

文献信息

• Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: Synthesis and biological properties
  作者：Jean-Sébastien Thomann、Fanny Monneaux、Gaëlle Creusat、Maria Vittoria Spanedda、Béatrice Heurtault、Chloé Habermacher、Francis Schuber、Line Bourel-Bonnet、Benoît Frisch

  DOI：10.1016/j.ejmech.2012.02.039

  日期：2012.5

  A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-alpha-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an alpha-Galactosylpyranose or an alpha-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (alpha/beta ratio > 9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. (C) 2012 Elsevier Masson SAS. All rights reserved.