N-(9-fluorenylmethyloxycarbonyl)-O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-D-serine | 211678-11-4

• 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: N-(9-fluorenylmethyloxycarbonyl)-O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-D-serine
• 英文别名: Fmoc-ser(alpha-mannose)OH；(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2S,3S,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxypropanoic acid
• CAS: 211678-11-4
• 化学式: C₃₂H₃₅NO₁₄
• 分子量: 657.628
• InChiKey: UGQPZVSWEMKXBN-BNORLHEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  47
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  199
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N-(9-fluorenylmethyloxycarbonyl)-O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-D-serine 在 吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 -L-glutamic acid 1-methylamide 5-benzyl ester
  参考文献：
  名称：

  Studies on Selectin Blockers. 7. Structure−Activity Relationships of Sialyl Lewis X Mimetics Based on Modified Ser-Glu Dipeptides

  摘要：

  We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(x), 1) and a 3'-sulfated Lewis X analogue (2) toward E-selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' beta-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' beta-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(x) mimetics with type II and type II'-beta-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

  DOI：

  10.1021/jm980267x
• 作为产物：
  描述：

  Α-D-五乙酸甘露糖酯 、 Fmoc-D-丝氨酸 在 三氟化硼乙醚 作用下， 以 氯仿 为溶剂， 反应 21.0h， 以45%的产率得到N-(9-fluorenylmethyloxycarbonyl)-O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-D-serine
  参考文献：
  名称：

  Studies on Selectin Blockers. 7. Structure−Activity Relationships of Sialyl Lewis X Mimetics Based on Modified Ser-Glu Dipeptides

  摘要：

  We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(x), 1) and a 3'-sulfated Lewis X analogue (2) toward E-selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' beta-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' beta-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(x) mimetics with type II and type II'-beta-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

  DOI：

  10.1021/jm980267x

文献信息

• A Solid-Phase Synthesis for β-Turn Mimetics of Sialyl Lewis X
  作者：Kiriko Kurokawa、Hiroshi Kumihara、Hirosato Kondo

  DOI：10.1016/s0960-894x(00)00358-9

  日期：2000.8

  A solid-phase synthesis of heterocyclic beta-turn mimetics of sialyl Lewis X, which is a natural carbohydrate ligand of selectins, was established. This synthetic method could be very useful for drug discovery of selectin antagonists using combinatorial chemistry techniques.

  建立了作为选择素的天然碳水化合物配体的唾液酸路易斯X的杂环β-转类似物的固相合成。这种合成方法对于使用组合化学技术发现选择素拮抗剂的药物可能非常有用。