Boc-Val-Leu-Phe-OMe | 863781-33-3

• 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: Boc-Val-Leu-Phe-OMe
• CAS: 863781-33-3
• 化学式: C₂₆H₄₁N₃O₆
• 分子量: 491.628
• InChiKey: NGGLLWAPPUWSLN-ACRUOGEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  35.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  122.83
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  Boc-Val-Leu-Phe-OMe 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 96.0h， 生成 (S)-2-((S)-4-Methyl-2-{(S)-3-methyl-2-[(S)-4-methyl-2-((S)-4-methyl-2-methylamino-pentanoylamino)-pentanoylamino]-butyrylamino}-pentanoylamino)-3-phenyl-propionic acid
  参考文献：
  名称：

  Sansalvamide A衍生物的合成及其在MSS结肠癌细胞系HT-29中的细胞毒性。

  摘要：

  我们报告了36种Sansalvamide A衍生物的合成及其对结肠癌HT-29细胞系（一种微卫星稳定（MSS）结肠癌细胞系）的生物活性。这三十六种化合物可分为三个子集，其中化合物的第一子集包含L-氨基酸，第二个子集包含D-氨基酸，而第三子集包含D-和L-氨基酸。五种化合物表现出出色的抑制活性（抑制率> 75％）。化合物的结构活性关系（SAR）确定了位置2或3上的单个D-氨基酸比Sansalvamide A肽的细胞毒性提高了10倍。这项工作强调了残基2和3的重要性以及D-氨基酸在该类化合物的非常规SAR中的作用。

  DOI：

  10.1016/j.bmc.2006.04.031
• 作为产物：
  描述：

  L-苯丙氨酸甲酯 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 Boc-Val-Leu-Phe-OMe
  参考文献：
  名称：

  用于合成Sansalvamide A衍生物的高产大环化条件

  摘要：

  描述了使用新的，高产的，原位脱保护-环化条件合成的九种Sansalvamide A衍生物，该条件对于该系列大环化合物而言是通用的，两个步骤的平均值均为55％。这是以前报道的产量的十倍。

  DOI：

  10.1016/j.tetlet.2005.11.056

文献信息

• Synthesis and Cytotoxicity of a New Class of Potent Decapeptide Macrocycles
  作者：Melinda R. Davis、Thomas J. Styers、Rodrigo A. Rodriguez、Po-Shen Pan、Robert C. Vasko、Shelli R. McAlpine

  DOI：10.1021/ol702403r

  日期：2008.1.1

  were made using a succinct convergent synthesis. These analogues share no structural homology to current cancer drugs, are cytotoxic at levels on par with existing drugs treating cancers, and demonstrate selectivity for drug-resistant pancreatic cancer cell lines over noncancerous cell lines. These molecules are excellent chemotherapeutic leads in the search for new anticancer agents.

  描述了五种十肽的合成，它们是天然五肽Sansalvamide A的C-2-对称衍生物。使用简洁的收敛性合成方法制得衍生物。这些类似物与目前的癌症药物没有结构同源性，在细胞毒性方面与现有的治疗癌症的药物相当，并且显示出对耐药性胰腺癌细胞系比非癌细胞系具有选择性。这些分子是寻找新的抗癌药的出色化学治疗方法。
• A comprehensive study of Sansalvamide A derivatives: The structure–activity relationships of 78 derivatives in two pancreatic cancer cell lines
  作者：Po-Shen Pan、Robert C. Vasko、Stephanie A. Lapera、Victoria A. Johnson、Robert P. Sellers、Chun-Chieh Lin、Chung-Mao Pan、Melinda R. Davis、Veronica C. Ardi、Shelli R. McAlpine

  DOI：10.1016/j.bmc.2009.07.017

  日期：2009.8

  first report of their activity against two pancreatic cancer cell lines. Our results show that out of 78 compounds, three compounds are worth pursuing as leads, as they show potency of ⩾55% in both cancer cell lines. These three compounds all have a common structural motif, two consecutive d-amino acids and an N-methyl moiety. Further, of these three compounds, two are second-generation structures, indicating

  我们报告了对两种胰腺癌细胞系有活性的 78 种化合物的广泛构效关系 (SAR)。我们对这些化合物的综合评估利用 SAR，使我们能够评估有效化合物的哪些特征对其细胞毒性起关键作用。这是 19 种新的第二代结构的首次报告，其中这些新化合物是从第一代 59 种化合物中设计出来的。测试了这 78 个结构的细胞毒性，这是它们对两种胰腺癌细胞系的活性的首次报告。我们的结果表明，在 78 种化合物中，有 3 种化合物值得作为先导物进行研究，因为它们在两种癌细胞系中都显示出 55% 的效力。这三种化合物都有一个共同的结构基序，两个连续的d-氨基酸和一个N-甲基部分。此外，在这三种化合物中，有两种是第二代结构，这表明我们可以合并和利用第一代的数据来设计第二代的效力。最后，一种类似物在中等纳摩尔范围内，并且在所有报道的 SAn A 衍生物中具有最低的 IC 50。这些类似物与当前的胰腺癌药物没有结构同源性，并
• Synthesis and Cytotoxicity of Novel Sansalvamide A Derivatives
  作者：Chris L. Carroll、Jennifer V. C. Johnston、Ahmet Kekec、Joseph D. Brown、Emily Parry、Julia Cajica、Irene Medina、Kristina M. Cook、Ricardo Corral、Po-Shen Pan、Shelli R. McAlpine

  DOI：10.1021/ol051161g

  日期：2005.8.1

  [GRAPHICS]Described are the syntheses of 14 derivatives of the natural product Sansalvamide A, where two are more active against HCT 116 colon cancer cell lines than the natural product. These derivatives were synthesized using a combinatorial-type strategy that permits elucidation of the amino acid role in the cytotoxicity, and they lay the groundwork for development of new anticancer agents.
• Synthesis of Second-Generation Sansalvamide A Derivatives: Novel Templates as Potential Antitumor Agents
  作者：Rodrigo A. Rodriguez、Po-Shen Pan、Chung-Mao Pan、Suchitra Ravula、Stephanie Lapera、Erinprit K. Singh、Thomas J. Styers、Joseph D. Brown、Julia Cajica、Emily Parry、Katerina Otrubova、Shelli R. McAlpine

  DOI：10.1021/jo061830j

  日期：2007.3.1

  We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.
• Comprehensive Study of Sansalvamide A Derivatives and their Structure–Activity Relationships against Drug-Resistant Colon Cancer Cell Lines
  作者：Katerina Otrubova、Gerald Lushington、David Vander Velde、Kathleen L. McGuire、Shelli R. McAlpine

  DOI：10.1021/jm070731a

  日期：2008.2.1

  We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating, multiple drug-resistant colon cancers.