N--L-asparaginsaeure-di-tert.-butylester | 700341-12-4

• 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--L-asparaginsaeure-di-tert.-butylester
• 英文别名: ditert-butyl (2S)-2-[[(4S)-4-amino-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]butanedioate
• CAS: 700341-12-4
• 化学式: C₂₁H₃₈N₂O₇
• 分子量: 430.542
• InChiKey: RMRSQBDXDJKGDJ-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N--L-asparaginsaeure-di-tert.-butylester 在 diethyl cyanophosphoridate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 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：

  Z-谷安酸叔丁基酯 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， -20.0 ℃ 、101.33 kPa 条件下， 反应 4.33h， 生成 N--L-asparaginsaeure-di-tert.-butylester
  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

文献信息

• Synthesis, computational docking and biological evaluation of celastrol derivatives as dual inhibitors of SERCA and P-glycoprotein in cancer therapy
  作者：Paolo Coghi、Jerome P.L. Ng、Onat Kadioglu、Betty Yuen Kwan Law、Alena Congling Qiu、Mohamed E.M. Saeed、Xi Chen、Chi Kio Ip、Thomas Efferth、Liang Liu、Vincent Kam Wai Wong

  DOI：10.1016/j.ejmech.2021.113676

  日期：2021.11

  celastrol derivatives was designed, synthesized, and evaluated for their in vitro cytotoxic activities against six human cancer cell lines (A549, HepG2, HepAD38, PC3, DLD-1 Bax-Bak WT and DKO) and three human normal cells (LO2, BEAS-2B, CCD19Lu). To our knowledge, six derivatives were the first example of dipeptide celastrol derivatives. Among them, compound 3 was the most promising derivative, as it

  设计、合成了一系列 11 种 Celastrol 衍生物，并评估了它们对 6 种人类癌细胞系（A549、HepG2、HepAD38、PC3、DLD-1 Bax-Bak WT 和 DKO）和三种人类正常细胞的体外细胞毒活性（ LO 2、BEAS-2B、CCD19Lu)。据我们所知，六种衍生物是二肽 celastrol 衍生物的第一个例子。其中，化合物3是最有前景的衍生物，因为它在肝癌HepAD38与人类正常肝细胞LO 2相比表现出显着的抗增殖活性和提高的选择性。化合物6在肝癌细胞中对人正常肺成纤维细胞、CCD19Lu 细胞系显示出更高的选择性。钙还在存在和不存在毒胡萝卜素的情况下评估了3和6 的2+动员，以证明它们对 SERCA 的抑制作用。发现衍生物3和6诱导LO 2、HepG2和HepAD38细胞的细胞凋亡。通过分子对接提出了所有合成的 celastrol 二肽和其他已知抑制剂的潜在对接姿势。最后，在
• Taschner,E. et al., Justus Liebigs Annalen der Chemie, 1961, vol. 646, p. 127 - 133
  作者：Taschner,E. et al.

  DOI：——

  日期：——
• 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)
  作者：Graham M. F. Bisset、Vassilios Bavetsias、Timothy J. Thornton、Krzysztof Pawelczak、A. Hilary Calvert、Leslie R. Hughes、Ann L. Jackman

  DOI：10.1021/jm00046a014

  日期：1994.9

  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.