methyl (S)-2-[(S)-2-(tert-butoxycarbonylamino)-N,4-dimethylpentanamido]-3-phenylpropanoate | 227616-01-5

• 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: methyl (S)-2-[(S)-2-(tert-butoxycarbonylamino)-N,4-dimethylpentanamido]-3-phenylpropanoate
• CAS: 227616-01-5
• 化学式: C₂₂H₃₄N₂O₅
• 分子量: 406.522
• InChiKey: XPYRMCKEMKAUJA-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  29.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  84.94
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-[(S)-2-(tert-butoxycarbonylamino)-N,4-dimethylpentanamido]-3-phenylpropanoate 以 水 为溶剂， 反应 0.17h， 生成 (3S,6S)-6-benzyl-3-isobutyl-1-methylpiperazine-2,5-dione
  参考文献：
  名称：

  N4-methylation changes the conformation of (3S,6S)-3-alkyl-6-benzylpiperazine-2,5-diones from folded to extended

  摘要：

  N4-methylation of (3S,6S)-3-alkyl-6-benzylpiperazine-2,5-diones (S,S)-1a-c was found to change their folded conformation to an extended conformation. Conformational aspects of N1- and/or N4-methylated (S,S)-1a-c were revealed by single crystal X-ray crystallography and H-1 NMR spectroscopy. (C) 2016 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2016.03.019
• 作为产物：
  描述：

  BOC-L-亮氨酸 、 N-Alpha-甲基-L-苯丙氨酸-甲酯盐酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 methyl (S)-2-[(S)-2-(tert-butoxycarbonylamino)-N,4-dimethylpentanamido]-3-phenylpropanoate
  参考文献：
  名称：

  N4-methylation changes the conformation of (3S,6S)-3-alkyl-6-benzylpiperazine-2,5-diones from folded to extended

  摘要：

  N4-methylation of (3S,6S)-3-alkyl-6-benzylpiperazine-2,5-diones (S,S)-1a-c was found to change their folded conformation to an extended conformation. Conformational aspects of N1- and/or N4-methylated (S,S)-1a-c were revealed by single crystal X-ray crystallography and H-1 NMR spectroscopy. (C) 2016 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2016.03.019

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。
• Solution-Phase Parallel Synthesis of a Pharmacophore Library of HUN-7293 Analogues:  A General Chemical Mutagenesis Approach To Defining Structure−Function Properties of Naturally Occurring Cyclic (Depsi)peptides
  作者：Yan Chen、Melitta Bilban、Carolyn A. Foster、Dale L. Boger

  DOI：10.1021/ja020166v

  日期：2002.5.1

  are detailed enlisting solution-phase techniques and simple acid-base liquid-liquid extractions for isolation and purification of intermediates and final products. Significant to the design of the studies and unique to solution-phase techniques, the library was assembled superimposing a divergent synthetic strategy onto a convergent total synthesis. An alanine scan and N-methyl deletion of each residue

  HUN-7293 (1) 是一种天然存在的环状七肽，是细胞粘附分子表达（VCAM-1、ICAM-1、E-选择素）的有效抑制剂，其过度表达是慢性炎症性疾病的特征。定义此类环状 (depsi) 肽的结构-功能关系的一般方法的代表，关键 HUN-7293 类似物的完整库的并行合成和评估是详细的采用液相技术和简单的酸碱液-液提取用于中间体和最终产品的分离和纯化。对于研究的设计和溶液相技术的独特性而言，该库的组装是将发散的合成策略叠加到收敛的全合成上。环七肽每个残基的丙氨酸扫描和 N-甲基缺失确定了负责或促成生物学特性的关键位点。同时制备一套完整的单个残基类似物进一步简化了结构，允许对 1 的每个结构特征进行评估，在单个研究中提供结构-功能关系的详细说明。在通过天然产物结构的系统化学诱变制备的药效团文库中，鉴定了具有可比效力的简化类似物，并且在某些情况下，提高了选择性。该文库的一个有效成员被证明是一种额外的天然产物，我们将其称为
• 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.