N-(N-Benzyloxycarbonyl-L-γ-glutamyl-1-tert.-butylester)-L-asparaginsaeure-di-tert.-butylester | 103777-98-6

• 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: N-(N-Benzyloxycarbonyl-L-γ-glutamyl-1-tert.-butylester)-L-asparaginsaeure-di-tert.-butylester
• 英文别名: Cbz-gGlu(OtBu)-Asp(OtBu)-OtBu；ditert-butyl (2S)-2-[[(4S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-4-(phenylmethoxycarbonylamino)pentanoyl]amino]butanedioate
• CAS: 103777-98-6
• 化学式: C₂₉H₄₄N₂O₉
• 分子量: 564.676
• InChiKey: YKYLLIOTDXDRSC-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  40
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(N-Benzyloxycarbonyl-L-γ-glutamyl-1-tert.-butylester)-L-asparaginsaeure-di-tert.-butylester 在 palladium on activated charcoal diethyl cyanophosphoridate 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 7.0h， 生成
  参考文献：
  名称：

  The Synthesis and Thymidylate Synthase Inhibitory Activity of L-.gamma.-L-Linked Dipeptide and L-.gamma.-Amide Analogs of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)

  摘要：

  Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.

  DOI：

  10.1021/jm00046a014
• 作为产物：
  描述：

  (S)-2-Benzyloxycarbonylamino-pentanedioic acid 5-methyl ester 生成 N-(N-Benzyloxycarbonyl-L-γ-glutamyl-1-tert.-butylester)-L-asparaginsaeure-di-tert.-butylester
  参考文献：
  名称：

  Taschner,E. et al., Justus Liebigs Annalen der Chemie, 1961, vol. 646, p. 127 - 133

  摘要：

  DOI：