Boc-N(Me)Leu-Leu-OMe | 109745-86-0

• 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-N(Me)Leu-Leu-OMe
• 英文别名: methyl (2S)-4-methyl-2-[[(2S)-4-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pentanoyl]amino]pentanoate
• CAS: 109745-86-0
• 化学式: C₁₉H₃₆N₂O₅
• 分子量: 372.505
• InChiKey: KFHXQMMXGJQGTI-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-N(Me)Leu-Leu-OMe 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 lithium hydroxide monohydrate 、 5%-palladium/activated carbon 、 水 、 氢气 、 甲酸铵 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 60.0h， 生成 (3R,6S,9S,12S,15R,18R,21S)-15-((R)-sec-butyl)-18-((R)-1-hydroxy-2-methylpropyl)-6,9-diisobutyl-1,3,4,10,12,13-hexamethyl-21-(4-(methylamino)butyl)-1,4,7,10,13,16,19-heptaazacyclohenicosane-2,5,8,11,14,17,20-heptaone
  参考文献：
  名称：

  Design, synthesis, and evaluation, derivatives of the fat-accumulation inhibitor ternatin: toward ternatin molecular probes

  摘要：

  Ternatin, a cyclic heptapeptide derived from mushroom, strongly inhibits fat accumulation in 3T3-L1 adipocytes. However, its mechanism of action remains unclear. In this Letter, we designed, synthesized, and evaluated its derivatives for use as molecular probes to isolate its target protein. Finally, we successfully established a pair of ternatin molecular probes. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.06.036
• 作为产物：
  描述：

  L-亮氨酸 在 氯化亚砜 、 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 Boc-N(Me)Leu-Leu-OMe
  参考文献：
  名称：

  Design, synthesis, and evaluation, derivatives of the fat-accumulation inhibitor ternatin: toward ternatin molecular probes

  摘要：

  Ternatin, a cyclic heptapeptide derived from mushroom, strongly inhibits fat accumulation in 3T3-L1 adipocytes. However, its mechanism of action remains unclear. In this Letter, we designed, synthesized, and evaluated its derivatives for use as molecular probes to isolate its target protein. Finally, we successfully established a pair of ternatin molecular probes. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.06.036

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。
• Convergent synthesis and in vivo inhibitory effect on fat accumulation of (−)-ternatin, a highly N-methylated cyclic peptide
  作者：Kenichiro Shimokawa、Kaoru Yamada、Masaki Kita、Daisuke Uemura

  DOI：10.1016/j.bmcl.2007.06.015

  日期：2007.8

  (-)-Ternatin (1), a highly N-methylated cyclic heptapeptide, is a potent inhibitor of fat accumulation against 3T3-LI murine adipocytes (EC50 = 0.14 mu g/mL) [Shimokawa, K.; Mashima, I.; Asai, A.; Yamada, K.; Kita, M.; Uemura, D. Tetrahedron Lett. 2006, 47, 4445]. Compound 1 was synthesized from Boc-protected amino acids in solution. Upon treatment with 1 at 5 mg/kg/day, increases in body weight and fat accumulation in high-fat-fied mice were both significantly suppressed. 0 2007 Elsevier Ltd. All rights reserved.

  (−)-Ternatin (1) 是一种高度N-甲基化的环状七肽，是针对 3T3-LI 小鼠脂肪细胞的强效脂肪积累抑制剂（EC50 = 0.14 μg/mL）[Shimokawa, K.; Mashima, I.; Asai, A.; Yamada, K.; Kita, M.; Uemura, D. Tetrahedron Lett. 2006, 47, 4445]。化合物 1 通过 Boc 保护的氨基酸在溶液中合成。在高脂饮食小鼠中，每天给予 5 mg/kg 的化合物 1 处理后，体重增加和脂肪积累均显著受到抑制。2007 Elsevier 有限公司。版权所有。
• Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A ternary complex
  作者：Jordan D Carelli、Steven G Sethofer、Geoffrey A Smith、Howard R Miller、Jillian L Simard、William C Merrick、Rishi K Jain、Nathan T Ross、Jack Taunton

  DOI：10.7554/elife.10222

  日期：——

  Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series of cyclic peptides with partially elucidated structures, we designed synthetic variants of ternatin, a cytotoxic and anti-adipogenic natural product whose molecular mode of action was unknown. The new ternatin variants are cytotoxic toward cancer cells, with up to 500-fold greater potency than ternatin itself. Using a ternatin photo-affinity probe, we identify the translation elongation factor-1A ternary complex (eEF1A·GTP·aminoacyl-tRNA) as a specific target and demonstrate competitive binding by the unrelated natural products, didemnin and cytotrienin. Mutations in domain III of eEF1A prevent ternatin binding and confer resistance to its cytotoxic effects, implicating the adjacent hydrophobic surface as a functional hot spot for eEF1A modulation. We conclude that the eukaryotic elongation factor-1A and its ternary complex with GTP and aminoacyl-tRNA are common targets for the evolution of cytotoxic natural products.

  环肽天然产物的发展利用了多种蛋白质靶标，其中许多靶标控制着重要的细胞过程。受一系列结构已部分阐明的环肽的启发，我们设计出了具有细胞毒性和抗脂肪生成作用的天然产品 ternatin 的合成变体，而这种天然产品的分子作用模式尚不清楚。新的燕麦素变体对癌细胞具有细胞毒性，其效力比燕麦素本身高出 500 倍。利用特纳丁的光亲和探针，我们确定了翻译延伸因子-1A 三元复合物（eEF1A-GTP-氨基酰-tRNA）为特异性靶标，并证明了与之无关的天然产物--didemnin 和 cytotrienin 的竞争性结合。eEF1A 结构域 III 的突变阻止了 ternatin 的结合，并使其对细胞毒性效应产生抗性，这表明邻近的疏水表面是 eEF1A 调节的功能热点。我们的结论是，真核生物伸长因子-1A及其与 GTP 和氨基酰-tRNA 的三元复合物是细胞毒性天然产物进化的共同目标。
• CYCLIC HEPTAPEPTIDE AND USE OF THE SAME
  申请人：National University Corporation Nagoya University

  公开号：EP2194062A1

  公开（公告）日：2010-06-09

  A novel cyclic heptapeptide that is useful as a preadipocyte differentiation-inhibitory agent or an adipocyte fat accumulation-inhibitory agent, and the use of such agents, are provided. A novel cyclic heptapeptide represented by the following formula is provided. wherein R is CH3, CH2CH(CH3)2, CH2OCH2C6H5, CH(OH)CH3, or CH2OH.

  提供了一种可用作前脂肪细胞分化抑制剂或脂肪细胞脂肪堆积抑制剂的新型环七肽及其用途。提供了由下式表示的一种新型环七肽。 其中 R 是 CH3、CH2CH(CH3)2、CH2OCH2C6H5、CH(OH)CH3 或 CH2OH。
• 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.