tert-butyl 3-[9H-fluoren-9-ylmethoxycarbonyl(methoxy)amino]propanoate | 247021-89-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: tert-butyl 3-[9H-fluoren-9-ylmethoxycarbonyl(methoxy)amino]propanoate
• CAS: 247021-89-2
• 化学式: C₂₃H₂₇NO₅
• 分子量: 397.471
• InChiKey: DYWYKJWRIVBLOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-[9H-fluoren-9-ylmethoxycarbonyl(methoxy)amino]propanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 魏因勒卜链接剂
  参考文献：
  名称：

  天冬氨酰肽醛的固相合成

  摘要：

  已经开发了一种高效固相合成天冬氨醛醛肽的方法。它使用低成本的合成方法来制备Fmoc保护的Weinreb酰胺连接基。该程序涵盖了几种四肽天冬氨酰醛以及生物素化的四肽天冬氨酰醛。

  DOI：

  10.1016/s0040-4039(00)01615-4
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 3-Methoxyamino-propionic acid tert-butyl ester; hydrochloride 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 tert-butyl 3-[9H-fluoren-9-ylmethoxycarbonyl(methoxy)amino]propanoate
  参考文献：
  名称：

  A Combinatorial Approach to the Identification of Dipeptide Aldehyde Inhibitors of β-Amyloid Production

  摘要：

  In an effort to rapidly identify potent inhibitors of A beta production and to probe the amino acid sequence specificity of the protease(s) responsible for the production of this peptide, a large number of dipeptide aldehydes were combinatorially synthesized and manually evaluated for their inhibitory properties. The starting point for this study was the dipeptide aldehyde carbobenzoxyl-valinyl-phenylalanal previously shown to inhibit the production of A beta in CHO cells stably transfected with the cDNA encoding beta APP695. Pools of related dipeptide aldehydes were combinatorially synthesized, and the most active pool was deconvoluted, resulting in the identification of the most active inhibitor of this pool. Systematic optimization of this inhibitor resulted in a series of dipeptide aldehydes with enhanced potencies relative to carbobenzoxylvalinyl-phenylalanal. The most active dipeptide aldehydes were those that possessed hydrophobic amino acids at both the P1 and P2 positions. The most potent compound identified in this study was 3,5-dimethoxycinnamamide-isoleucinyl-leucinal with an IC50 of 9.6 mu M, approximately 10-fold more active than carbobenzoxyl-valinyl-phenylalanal. In immunoprecipitation experiments using antibodies directed toward either A beta 1-40 or A beta 1-42, 3,5-dimethoxycinnamamide-isoleucinyl-leucinal, like carbobenzoxyl-valinyl-phenylalanal, preferentially inhibited the shorter 1-40 form of A beta, whereas the longer 1-42 form was not as strongly inhibited. These results suggest that dipeptide aldehydes related to carbobenzoxyl-valinyl-phenylalanal inhibit A beta through similar mechanisms and demonstrate the utility of a combinatorial synthesis approach to rapidly identify potent inhibitors of A beta production.

  DOI：

  10.1021/jm990009f