HO-Pro-Oxazole-Thiazole-Pro-Leu-NHBoc | 1361053-47-5

• 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: HO-Pro-Oxazole-Thiazole-Pro-Leu-NHBoc
• CAS: 1361053-47-5
• 化学式: C₂₇H₃₇N₅O₇S
• 分子量: 575.686
• InChiKey: GNCATWXDJURSPH-VDGAXYAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  155.17
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  HO-Pro-Oxazole-Thiazole-Pro-Leu-NHBoc 在 双氧水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 (12S,22Z,32Z,52S,122Z,8R,11S,15S)-8-benzyl-15-isobutyl-11-methyl-7,10,14-triaza-3(2,4)-oxazola-2,12(2,4)-dithiazola-1(2,1),5(1,2)-dipyrrolidinacyclohexadecaphane-4,6,9,13,16-pentaone
  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-bromo-1,1-dimethoxyethyl)-1,3-oxazole-4-carboxylate 在 吡啶 、 甲酸 、 lithium hydroxide monohydrate 、 双氧水 、 potassium carbonate 、 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-) 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 34.25h， 生成 HO-Pro-Oxazole-Thiazole-Pro-Leu-NHBoc
  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

• Synthesis, Structure–Activity Analysis, and Biological Evaluation of Sanguinamide B Analogues
  作者：Hendra Wahyudi、Worawan Tantisantisom、Xuechao Liu、Deborah M. Ramsey、Erinprit K. Singh、Shelli R. McAlpine

  DOI：10.1021/jo3017499

  日期：2012.12.7

  We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only L- and D-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation. Testing of all conformer analogues showed that inclusion of an L- or D-Phe was a superior design element than incorporating the N-Me moiety that is often utilized to control macrocyclic conformation. Finally, we show that there is an ideal Phe residue (in this case L-Phe) for generating compounds that have the greatest inhibitory effect on bacterial motility. Our data support the hypothesis that the macrocyclic conformation is dictated by the benzyl moiety requiring a "pseudoequatorial" position, and all other energy considerations are secondary.
• 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
• Mechanistic Studies of Sanguinamide B Derivatives: A Unique Inhibitor of Eukaryotic Ribosomes
  作者：Worawan Tantisantisom、Deborah M. Ramsey、Shelli R. McAlpine

  DOI：10.1021/ol401749p

  日期：2013.9.20

  Described are mechanistic studies of two Sanguinamide B (San B) derivatives. These compounds were identified as eukaryotic ribosomal inhibitors. Two biotinylated San B derivatives were synthesized and used to capture protein targets in a pull-down assay. LC/MS/MS analysis of the San B-captured targets identified several proteins that comprise eukaryotic ribosomal subunits. The translation inhibitory effect of San B was confirmed using an in vitro translation assay. Moreover, an evaluation of cell death mechanisms is reported.