D-(N-tert-butoxycarbonylalanyl)-L-phenylalanine | 94883-19-9

• 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: D-(N-tert-butoxycarbonylalanyl)-L-phenylalanine
• 英文别名: (2S)-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-3-phenylpropanoic acid
• CAS: 94883-19-9
• 化学式: C₁₇H₂₄N₂O₅
• 分子量: 336.388
• InChiKey: VAMUDINSUBSTNS-YPMHNXCESA-N

物化性质

• 沸点：
  566.1±50.0 °C(Predicted)
• 密度：
  1.182±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  D-(N-tert-butoxycarbonylalanyl)-L-phenylalanine 在 N-甲基吗啉 、 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 Boc-Tyr-D-Ala-Phe-Asp(OtBu)-Val-Val-Gly-OEt
  参考文献：
  名称：

  Unique sequence in deltorphin C confers structural requirement for δ opioid receptor selectivity

  摘要：

  A series of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues were synthesized to assess the consequences of changing anionic and hydrophobic residues on delta receptor selectivity. Analogues with altered C-terminal groups, inverted sequences, or esterified with tert-butyl, benzyl, or ethyl groups revealed that high delta selectivity required an unmodified amino acid sequence. Shifts of Asp and hydrophobic residues decreased delta selectivity due to loss in delta affinity (5- to almost-equal-to 700-fold); mu affinity was unchanged or increased 14-fold. Suppression of charge or deamidation diminished delta selectivity through reduced delta and modified mu affinities. Data provide evidence that a negative charge does not a priori guarantee high selectivity and specific alignment of anionic and hydrophobic residues might facilitate optimum spatial configuration which complements the 8 receptor binding site.

  DOI：

  10.1016/0223-5234(92)90113-f
• 作为产物：
  描述：

  Boc-D-Ala-Phe-OMe 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 1.0h， 生成 D-(N-tert-butoxycarbonylalanyl)-L-phenylalanine
  参考文献：
  名称：

  An Approach Towards More Selective Anticancer Agents

  摘要：

  一种有前景的方法是利用与人类恶性肿瘤相关的蛋白酶增强表达来更好地靶向抗癌药物治疗。特别是，已经发现纤溶酶原激活剂的活性显著提高，导致丝氨酸蛋白酶纤溶酶的活性增加。双功能烷基化剂，如N-(2-氯乙基)-N-亚硝基脲，显示出广泛的抗癌活性，但也表现出相当大的全身毒性。我们在这里描述了一种新型N-亚硝基脲类前药的合成，这些前药设计为通过肿瘤相关的蛋白酶激活，以提供增强的抗肿瘤活性和减少的全身毒性。代表纤溶酶底物的三肽通过酰胺键连接到N’-(2-氨基乙基)-N-(2-氯乙基)-N-亚硝基脲及相应的N’-甲基衍生物。我们描述了这些新三肽结合物的合成和纤溶酶触发的分解。表达高纤溶酶原激活剂活性的癌细胞在纤溶酶原存在的情况下对新前药高度敏感，但在缺乏的情况下则不然。

  DOI：

  10.1055/s-1996-4368

文献信息

• Unique sequence in deltorphin C confers structural requirement for δ opioid receptor selectivity
  作者：LH Lazarus、S Salvadori、P Grieco、WE Wilson、R Tomatis

  DOI：10.1016/0223-5234(92)90113-f

  日期：1992.11

  A series of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues were synthesized to assess the consequences of changing anionic and hydrophobic residues on delta receptor selectivity. Analogues with altered C-terminal groups, inverted sequences, or esterified with tert-butyl, benzyl, or ethyl groups revealed that high delta selectivity required an unmodified amino acid sequence. Shifts of Asp and hydrophobic residues decreased delta selectivity due to loss in delta affinity (5- to almost-equal-to 700-fold); mu affinity was unchanged or increased 14-fold. Suppression of charge or deamidation diminished delta selectivity through reduced delta and modified mu affinities. Data provide evidence that a negative charge does not a priori guarantee high selectivity and specific alignment of anionic and hydrophobic residues might facilitate optimum spatial configuration which complements the 8 receptor binding site.
• An Approach Towards More Selective Anticancer Agents
  作者：G. Eisenbrand、S. Lauck-Birkel、W. C. Tang

  DOI：10.1055/s-1996-4368

  日期：1996.10

  A promising approach towards better targeted anticancer drug therapy takes advantage of enhanced expression of proteases associated with human malignancies. Especially plasminogen activator activity has been found to be substantially increased, leading to an enhanced activity of the serine protease plasmin. Bifunctional alkylating agents, such as N-(2-chloroethyl)-N-nitrosoureas, display broad spectrum anticancer activity, but also exhibit considerable systemic toxicity. We describe here the synthesis of new N-nitrosourea-based prodrugs designed to become activated by tumor-associated proteases, to provide for enhanced antitumor activity and reduced systemic toxicity. Tripeptides representing substrates for plasmin were linked by an amide bond to N’-(2-aminoethyl)-N-(2-chloroethyl)-N-nitrosourea and the corresponding N’-methyl derivative. Synthesis and plasmin-triggered decomposition of these new tripeptide conjugates is described. Cancer cells expressing high plasminogen activator activity are highly sensitive to the new prodrugs in the presence of plasminogen, but not in its absence.

  一种有前景的方法是利用与人类恶性肿瘤相关的蛋白酶增强表达来更好地靶向抗癌药物治疗。特别是，已经发现纤溶酶原激活剂的活性显著提高，导致丝氨酸蛋白酶纤溶酶的活性增加。双功能烷基化剂，如N-(2-氯乙基)-N-亚硝基脲，显示出广泛的抗癌活性，但也表现出相当大的全身毒性。我们在这里描述了一种新型N-亚硝基脲类前药的合成，这些前药设计为通过肿瘤相关的蛋白酶激活，以提供增强的抗肿瘤活性和减少的全身毒性。代表纤溶酶底物的三肽通过酰胺键连接到N’-(2-氨基乙基)-N-(2-氯乙基)-N-亚硝基脲及相应的N’-甲基衍生物。我们描述了这些新三肽结合物的合成和纤溶酶触发的分解。表达高纤溶酶原激活剂活性的癌细胞在纤溶酶原存在的情况下对新前药高度敏感，但在缺乏的情况下则不然。