methyl (2S,4S,5R,6R)-4-acetyloxy-2-[(2R,3S,4S,5R,6S)-5-acetyloxy-2-(acetyloxymethyl)-6-[(2R,3R,4S,5R,6R)-4,5-diacetyloxy-2-(acetyloxymethyl)-6-azidooxan-3-yl]oxy-3-hydroxyoxan-4-yl]oxy-6-[(1S,2R)-1,2,3-triacetyloxypropyl]-5-[(2,2,2-trifluoroacetyl)amino]oxane-2-carboxylate | 827608-21-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (2S,4S,5R,6R)-4-acetyloxy-2-[(2R,3S,4S,5R,6S)-5-acetyloxy-2-(acetyloxymethyl)-6-[(2R,3R,4S,5R,6R)-4,5-diacetyloxy-2-(acetyloxymethyl)-6-azidooxan-3-yl]oxy-3-hydroxyoxan-4-yl]oxy-6-[(1S,2R)-1,2,3-triacetyloxypropyl]-5-[(2,2,2-trifluoroacetyl)amino]oxane-2-carboxylate
• CAS: 827608-21-9
• 化学式: C₄₂H₅₅F₃N₄O₂₇
• 分子量: 1104.9
• InChiKey: NUCMUYNAGKSLSC-SAASAMEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  76
• 可旋转键数：
  31
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  373
• 氢给体数：
  2
• 氢受体数：
  32

反应信息

• 作为反应物：
  描述：

  methyl (2S,4S,5R,6R)-4-acetyloxy-2-[(2R,3S,4S,5R,6S)-5-acetyloxy-2-(acetyloxymethyl)-6-[(2R,3R,4S,5R,6R)-4,5-diacetyloxy-2-(acetyloxymethyl)-6-azidooxan-3-yl]oxy-3-hydroxyoxan-4-yl]oxy-6-[(1S,2R)-1,2,3-triacetyloxypropyl]-5-[(2,2,2-trifluoroacetyl)amino]oxane-2-carboxylate 在 sodium hydroxide 、 Lindlar's catalyst 、 氢气 、 臭氧 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 21.67h， 生成 N-{O-[5-phenylacetamido-3,5-dideoxy-D-glycero-α-D-galacto-non-2-ulopyranosylonic acid]-(2-3)-O-(β-D-galactopyranosyl)-(1-4)-β-D-glucopyranosyl} 4-oxobutanamide
  参考文献：
  名称：

  Synthesis and Immunological Properties of N-Modified GM3 Antigens as Therapeutic Cancer Vaccines

  摘要：

  The problem of immunotolerance to GM3, an important tumor-associated trisaccharide antigen, seriously hinders its usage in cancer vaccine development. To solve this problem, the keyhole limpet hemocyanin (KLH) conjugates of a series of GM3 derivatives were synthesized and screened as therapeutic cancer vaccines. First, the beta-linked anomeric azides of differently N-acylated GM3 analogues were prepared by a highly convergent procedure. Next, a pentenoyl group was linked to the reducing end of the carbohydrate antigens following selective reduction of the azido group. The linker was thereafter ozonolyzed to give an aldehyde functionality permitting the conjugation of the antigens to KLH via reductive amination. Finally, the immunological properties of the resultant glycoconjugates were studied in C57BL/6 mice by assessing the titers of specific antibodies induced by the GM3 analogues. While KLH-GM3 elicited low levels of immune response, the KLH conjugates of N-propionyl, N-butanoyl, N-isobutanoyl, and N-phenylacetyl GM3s induced robust immune reactions with antibodies of multiple isotypes, indicating significantly improved and T-cell dependent immune responses that lead to isotype switching, affinity maturation, and the induction of immunological "memory". It was suggested that GM3PhAc-KLH is a promising vaccine candidate for glycoengineered immunotherapy of cancer with GM3 as the primary target.

  DOI：

  10.1021/jm0494422
• 作为产物：
  描述：

  O-(2,6-di-O-acetyl-β-D-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-β-D-glucopyranosyl azide 、 methyl (ethyl 4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-5-trifluoroacetamido-D-glycero-D-galacto-non-2-ulopyranosid)onate 在 4 A molecular sieve 、 N-碘代丁二酰亚胺 、 三氟甲磺酸 作用下， 以 乙腈 为溶剂， 反应 21.0h， 生成 methyl (2S,4S,5R,6R)-4-acetyloxy-2-[(2R,3S,4S,5R,6S)-5-acetyloxy-2-(acetyloxymethyl)-6-[(2R,3R,4S,5R,6R)-4,5-diacetyloxy-2-(acetyloxymethyl)-6-azidooxan-3-yl]oxy-3-hydroxyoxan-4-yl]oxy-6-[(1S,2R)-1,2,3-triacetyloxypropyl]-5-[(2,2,2-trifluoroacetyl)amino]oxane-2-carboxylate
  参考文献：
  名称：

  Synthesis and Immunological Properties of N-Modified GM3 Antigens as Therapeutic Cancer Vaccines

  摘要：

  The problem of immunotolerance to GM3, an important tumor-associated trisaccharide antigen, seriously hinders its usage in cancer vaccine development. To solve this problem, the keyhole limpet hemocyanin (KLH) conjugates of a series of GM3 derivatives were synthesized and screened as therapeutic cancer vaccines. First, the beta-linked anomeric azides of differently N-acylated GM3 analogues were prepared by a highly convergent procedure. Next, a pentenoyl group was linked to the reducing end of the carbohydrate antigens following selective reduction of the azido group. The linker was thereafter ozonolyzed to give an aldehyde functionality permitting the conjugation of the antigens to KLH via reductive amination. Finally, the immunological properties of the resultant glycoconjugates were studied in C57BL/6 mice by assessing the titers of specific antibodies induced by the GM3 analogues. While KLH-GM3 elicited low levels of immune response, the KLH conjugates of N-propionyl, N-butanoyl, N-isobutanoyl, and N-phenylacetyl GM3s induced robust immune reactions with antibodies of multiple isotypes, indicating significantly improved and T-cell dependent immune responses that lead to isotype switching, affinity maturation, and the induction of immunological "memory". It was suggested that GM3PhAc-KLH is a promising vaccine candidate for glycoengineered immunotherapy of cancer with GM3 as the primary target.

  DOI：

  10.1021/jm0494422