Boc-N(Me)Leu-Leu-OH | 863781-44-6

• 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-N(Me)Leu-Leu-OH
• 英文别名: (2S)-4-methyl-2-[[(2S)-4-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pentanoyl]amino]pentanoic acid
• CAS: 863781-44-6
• 化学式: C₁₈H₃₄N₂O₅
• 分子量: 358.478
• InChiKey: DOMCNVRMIWDDCA-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-N(Me)Leu-Leu-OH 在 N,N-二异丙基乙胺 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-) 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 98.0h， 生成 cyclo[N(Me)Leu-Leu-Val-Leu-Phe]
  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：

  Boc-N-Me-L-Leu-L-Leu-OBn 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 Boc-N(Me)Leu-Leu-OH
  参考文献：
  名称：

  d-氨基酸位置影响Galaxamide类似物的抗癌活性：细胞凋亡机制研究。

  摘要：

  Galaxamide是一种来自Galaxaurafilosa的提取物，是一种含有五种l-亮氨酸的环状五肽。由于特殊的环状结构和优异的抗癌活性，Galaxamide及其类似物的合成及其后续的生物应用引起了极大的关注。在目前的工作中，我们通过用苯丙氨酸代替一个亮氨酸取代了一个L-亮氨酸，并改变了d-氨基酸的位置，从而合成了六个Galaxamide类似物。测试了合成的Galaxamide类似物对四种体外人类癌细胞系，人类肝细胞细胞（HepG2），人类乳腺癌细胞（MCF-7），人类乳腺癌细胞（MDA-MB-435）的抗癌作用。宫颈癌细胞系（Hela）。结果表明，具有不同d-氨基酸位置的Galaxamide类似物显示出独特的抗癌潜力。在位置5（Analog-6）上含有d-氨基酸的Galaxamide类似物具有最强的抗癌活性。机制研究表明，Analog-6可能通过抑制HepG2细胞在细胞周期亚G1期的

  DOI：

  10.3390/ijms18030544

文献信息

• 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.
• 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。
• d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study
  作者：Defa Bai、Siming Yu、Shenghui Zhong、Bingxin Zhao、Shaoling Qiu、Jianwei Chen、Jignesh Lunagariya、Xiaojian Liao、Shihai Xu

  DOI：10.3390/ijms18030544

  日期：——

  cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro

  Galaxamide是一种来自Galaxaurafilosa的提取物，是一种含有五种l-亮氨酸的环状五肽。由于特殊的环状结构和优异的抗癌活性，Galaxamide及其类似物的合成及其后续的生物应用引起了极大的关注。在目前的工作中，我们通过用苯丙氨酸代替一个亮氨酸取代了一个L-亮氨酸，并改变了d-氨基酸的位置，从而合成了六个Galaxamide类似物。测试了合成的Galaxamide类似物对四种体外人类癌细胞系，人类肝细胞细胞（HepG2），人类乳腺癌细胞（MCF-7），人类乳腺癌细胞（MDA-MB-435）的抗癌作用。宫颈癌细胞系（Hela）。结果表明，具有不同d-氨基酸位置的Galaxamide类似物显示出独特的抗癌潜力。在位置5（Analog-6）上含有d-氨基酸的Galaxamide类似物具有最强的抗癌活性。机制研究表明，Analog-6可能通过抑制HepG2细胞在细胞周期亚G1期的