Boc-L-Val-D-Phe-L-Phe-OMe | 934715-31-8

• 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: Boc-L-Val-D-Phe-L-Phe-OMe
• 英文别名: Boc-Val-D-Phe-Phe-OMe；methyl (2S)-2-[[(2R)-2-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoate
• CAS: 934715-31-8
• 化学式: C₂₉H₃₉N₃O₆
• 分子量: 525.645
• InChiKey: VZBNFTXNTUPFEP-SGNDLWITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Boc-L-Val-D-Phe-L-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-) 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 生成 cyclo[Leu-Leu-Val-D-Phe-Phe]
  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 ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate 、 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 7.16h， 生成 Boc-L-Val-D-Phe-L-Phe-OMe
  参考文献：
  名称：

  异手性三肽的晶体结构和超分子排列

  摘要：

  研究了末端保护的 Boc-Val-Phe-Phe-OMe 的所有可能立体异构体的自组装特性，与阿尔茨海默氏淀粉样蛋白-β (Aβ 18-20 ) 肽具有序列同质性。场发射扫描显微镜（FE-SEM）的形态分析表明，受保护的 VFF 和 vff（小写字母表示d 的一个字母代码）-氨基酸）表现出带状纤维网络，vFF、Vff、VfF和vFf形成棒状结构。尽管 VFf 表现出两种形态（棒状和球形）的混合，但 vfF 主要显示球形结构。单晶 X 射线衍射 (SC-XRD) 表明五个立体异构体形成平行的β-折叠排列。在高阶包装中，Vff、VfF 和 vFf 表现出超分子片状结构，而 VFf 和 vfF 对则表现出螺旋片状排列。所有相应的对映异构体都显示出相同的形态但相反的构象。肽中氨基酸的手性在其超分子排列中起着重要作用。有趣的是，所有自聚集肽都可以与淀粉样蛋白结合染料硫黄素 T 结合。

  DOI：

  10.1002/pep2.24229

文献信息

• 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.
• Crystal structure and supramolecular arrangement of heterochiral tripeptides
  作者：Gobinda Dolai、Rajat Subhra Giri、Sayanta Roy、Bhubaneswar Mandal

  DOI：10.1002/pep2.24229

  日期：2021.11

  VfF, and vFf formed rod-like structures. Although VFf exhibited a mixture of two morphologies (rod-like and spherical), vfF showed spherical structures predominantly. The single-crystal X-ray diffraction (SC-XRD) indicated that five of the stereoisomers formed a parallel beta-sheet arrangement. In higher-order packing, while Vff, VfF, and vFf exhibited supramolecular sheet-like architecture, VFf and

  研究了末端保护的 Boc-Val-Phe-Phe-OMe 的所有可能立体异构体的自组装特性，与阿尔茨海默氏淀粉样蛋白-β (Aβ 18-20 ) 肽具有序列同质性。场发射扫描显微镜（FE-SEM）的形态分析表明，受保护的 VFF 和 vff（小写字母表示d 的一个字母代码）-氨基酸）表现出带状纤维网络，vFF、Vff、VfF和vFf形成棒状结构。尽管 VFf 表现出两种形态（棒状和球形）的混合，但 vfF 主要显示球形结构。单晶 X 射线衍射 (SC-XRD) 表明五个立体异构体形成平行的β-折叠排列。在高阶包装中，Vff、VfF 和 vFf 表现出超分子片状结构，而 VFf 和 vfF 对则表现出螺旋片状排列。所有相应的对映异构体都显示出相同的形态但相反的构象。肽中氨基酸的手性在其超分子排列中起着重要作用。有趣的是，所有自聚集肽都可以与淀粉样蛋白结合染料硫黄素 T 结合。
• 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.