Boc-D-Leu-N(Me)Leu-Val-Leu-D-Phe-OMe | 934715-25-0

• 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-D-Leu-N(Me)Leu-Val-Leu-D-Phe-OMe
• 英文别名: methyl (2R)-2-[[(2S)-4-methyl-2-[[(2S)-3-methyl-2-[[(2S)-4-methyl-2-[methyl-[(2R)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]pentanoyl]amino]butanoyl]amino]pentanoyl]amino]-3-phenylpropanoate
• CAS: 934715-25-0
• 化学式: C₃₉H₆₅N₅O₈
• 分子量: 731.974
• InChiKey: FETLSZVYEWBSSK-VYDZHMBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  52
• 可旋转键数：
  22
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  172
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Boc-D-Leu-N(Me)Leu-Val-Leu-D-Phe-OMe 在 盐酸 作用下， 以 四氢呋喃 、 苯甲醚 为溶剂， 反应 48.0h， 生成 2-[2-(2-{2-[(2-amino-4-methyl-pentanoyl)-methyl-amino]-4-methyl-pentanoylamino}-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-3-phenyl-propionic acid
  参考文献：
  名称：

  一类新型强十肽大环化合物的合成和细胞毒性。

  摘要：

  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。

  DOI：

  10.1021/ol702403r
• 作为产物：
  描述：

  BOC-D-亮氨酸 在 lithium hydroxide 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 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 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 Boc-D-Leu-N(Me)Leu-Val-Leu-D-Phe-OMe
  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

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.
• 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.
• 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。