methyl (2S)-1-[2-[2-[(2S)-1-[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]pyrrolidin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carbonyl]pyrrolidine-2-carboxylate | 1361053-60-2

• 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 (2S)-1-[2-[2-[(2S)-1-[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]pyrrolidin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carbonyl]pyrrolidine-2-carboxylate
• CAS: 1361053-60-2
• 化学式: C₂₈H₃₉N₅O₇S
• 分子量: 589.713
• InChiKey: AHRGOCIZNZXKAJ-YYWHXJBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  172
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl (2S)-1-[2-[2-[(2S)-1-[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]pyrrolidin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carbonyl]pyrrolidine-2-carboxylate 在 双氧水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-((S)-1-((R)-2-((S)-1-(2-(2-((S)-1-((tert-butoxycarbonyl)-L-leucyl)pyrrolidin-2-yl)thiazol-4-yl)oxazole-4-carbonyl)pyrrolidine-2-carboxamido)-3-phenylpropanamido)ethyl)thiazole-4-carboxylic acid
  参考文献：
  名称：

  Sanguinamide B analogs: identification of active macrocyclic structures

  摘要：

  We report the synthesis of three new sanguinamide B (San B) analogs. We substituted in amino acids along the San B backbone with an N-Me, glycine, or an aromatic moiety (Phe or D-Phe) generating twelve derivatives in total. Testing in HCT-116 colon cancer cell lines resulted in establishing a structure-activity relationship. Our data show that the substitution of L- or D-Phe adjacent to the thiazole in the San B backbone locks the macrocycle into a single conformer, but only D-Phe analogs are cytotoxic. We demonstrate that the conformation of the macrocycle is extremely sensitive to stereochemistry and amino acid placement. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.02.106
• 作为产物：
  描述：

  methyl 2-(2-((S)-1-((tert-butoxycarbonyl)-L-leucyl)pyrrolidin-2-yl)thiazol-4-yl)oxazole-4-carboxylate 在 lithium hydroxide monohydrate 、 双氧水 、 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 、 水 为溶剂， 生成 methyl (2S)-1-[2-[2-[(2S)-1-[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]pyrrolidin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carbonyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  反式，反式Sanguinamide B和构象异构体的全合成

  摘要：

  报道了通过有效的合成策略制备的血红素酰胺B的第一个全合成。天然产物，反式，反式- Sanguinamide B（1），在具有热力学率，生成了反式，顺式-Sanguinamide B（2）和顺式，顺式- Sanguinamide B（3）。顺式，顺式Sanguinamide B构象异构体（3）完全转化为天然产物（1）和反式，顺式构象异构体（2）完全转化通过加热到170°C达到）。生物学评估表明，Sanguinamide B构象异构体破坏了铜绿假单胞菌中一种毒性决定簇的活性。

  DOI：

  10.1021/ol203290n

文献信息

• Total Synthesis of <i>trans</i>,<i>trans-</i>Sanguinamide B and Conformational Isomers
  作者：Erinprit K. Singh、Deborah M. Ramsey、Shelli R. McAlpine

  DOI：10.1021/ol203290n

  日期：2012.3.2

  The first total synthesis of Sanguinamide B is reported, prepared via an efficient synthetic strategy. The natural product, trans,trans-Sanguinamide B (1), was generated in a thermodynamic ratio with trans,cis-Sanguinamide B (2) and cis,cis-Sanguinamide B (3). Complete conversion of the cis,cis-Sanguinamide B conformer (3) to the natural product (1) and the trans,cis- conformer (2) was achieved by

  报道了通过有效的合成策略制备的血红素酰胺B的第一个全合成。天然产物，反式，反式- Sanguinamide B（1），在具有热力学率，生成了反式，顺式-Sanguinamide B（2）和顺式，顺式- Sanguinamide B（3）。顺式，顺式Sanguinamide B构象异构体（3）完全转化为天然产物（1）和反式，顺式构象异构体（2）完全转化通过加热到170°C达到）。生物学评估表明，Sanguinamide B构象异构体破坏了铜绿假单胞菌中一种毒性决定簇的活性。
• Synthesis of macrocycles that inhibit protein synthesis: stereochemistry and structural based studies on sanguinamide B derivatives
  作者：Adrian L. Pietkiewicz、Hendra Wahyudi、Jeanette R. McConnell、Shelli R. McAlpine

  DOI：10.1016/j.tetlet.2014.10.089

  日期：2014.12
• Sanguinamide B analogs: identification of active macrocyclic structures
  作者：Hendra Wahyudi、Worawan Tantisantisom、Shelli R. McAlpine

  DOI：10.1016/j.tetlet.2014.02.106

  日期：2014.4

  We report the synthesis of three new sanguinamide B (San B) analogs. We substituted in amino acids along the San B backbone with an N-Me, glycine, or an aromatic moiety (Phe or D-Phe) generating twelve derivatives in total. Testing in HCT-116 colon cancer cell lines resulted in establishing a structure-activity relationship. Our data show that the substitution of L- or D-Phe adjacent to the thiazole in the San B backbone locks the macrocycle into a single conformer, but only D-Phe analogs are cytotoxic. We demonstrate that the conformation of the macrocycle is extremely sensitive to stereochemistry and amino acid placement. (C) 2014 Elsevier Ltd. All rights reserved.