H-D-Val-Leu-Phe-OMe | 934715-57-8

• 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: H-D-Val-Leu-Phe-OMe
• 英文别名: methyl (2S)-2-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoate
• CAS: 934715-57-8
• 化学式: C₂₁H₃₃N₃O₄
• 分子量: 391.511
• InChiKey: FJFLMLFTLXQEIB-OKZBNKHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  H-D-Val-Leu-Phe-OMe 在 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Synthesis of Second-Generation Sansalvamide A Derivatives: Novel Templates as Potential Antitumor Agents

  摘要：

  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.

  DOI：

  10.1021/jo061830j
• 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 4.0h， 生成 H-D-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 of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29
  作者：Thomas J. Styers、Ahmet Kekec、Rodrigo Rodriguez、Joseph D. Brown、Julia Cajica、Po-Shen Pan、Emily Parry、Chris L. Carroll、Irene Medina、Ricardo Corral、Stephanie Lapera、Katerina Otrubova、Chung-Mao Pan、Kathleen L. McGuire、Shelli R. McAlpine

  DOI：10.1016/j.bmc.2006.04.031

  日期：2006.8

  thirty-six Sansalvamide A derivatives, and their biological activity against colon cancer HT-29 cell line, a microsatellite stable (MSS) colon cancer cell-line. The thirty-six compounds can be divided into three subsets, where the first subset of compounds contains L-amino acids, the second subset contains D-amino acids, and the third subset contains both D- and L-amino acids. Five compounds exhibited

  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。
• High-yielding macrocyclization conditions used in the synthesis of novel Sansalvamide A derivatives
  作者：Thomas J. Styers、Rodrigo Rodriguez、Po-Shen Pan、Shelli R. McAlpine

  DOI：10.1016/j.tetlet.2005.11.056

  日期：2006.1

  Described are the syntheses of nine Sansalvamide A derivatives using new, high-yielding, in situ deprotection–cyclization conditions that are general for this series of macrocycles, 55% average for both steps. This is 10-fold greater than previously reported yields.

  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。
• 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。
• 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.
• 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.