(S)-ethyl 2-(1-(tert-butoxycarbonylamino)-2-phenylethyl)thiazole-4-carboxylate | 131148-64-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-ethyl 2-(1-(tert-butoxycarbonylamino)-2-phenylethyl)thiazole-4-carboxylate
• 英文别名: EtO-Thiazole-Phe-NHBoc；Boc-Phe-Th-OEt；ethyl 2-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylethyl]-1,3-thiazole-4-carboxylate
• CAS: 131148-64-6
• 化学式: C₁₉H₂₄N₂O₄S
• 分子量: 376.477
• InChiKey: AJXGZGUHMAVQBN-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-ethyl 2-(1-(tert-butoxycarbonylamino)-2-phenylethyl)thiazole-4-carboxylate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 3.0h， 生成 EtO-Thiazole-Phe-NH2
  参考文献：
  名称：

  用于多功能偶联的新型dolastatin 10衍生物的合成和评估

  摘要：

  Dolastatin 10（1）是一种高效的细胞毒性微管抑制剂（细胞毒性IC 50  <5.0 nM），其几种类似物最近已被用作抗体药物偶联物中的有效载荷。在本文中，我们描述了一系列新颖的dolastatin 10类似物的设计和合成，这些类似物可用作结合药物的有效载荷。我们探索了在C的噻唑部分含有官能团的类似物-dolastatin 10的末端。官能团包括胺，醇和硫醇，它们是已知结合药物中使用的代表性结构。这些新颖的类似物在肿瘤细胞增殖试验中显示出出色的功效，因此，该系列的dolastatin 10类似物适合用作缀合药物中的通用有效负载。还讨论了对类似物的结构-活性关系的见解。

  DOI：

  10.1016/j.bmc.2018.02.011
• 作为产物：
  描述：

  L-苯丙氨酰胺盐酸盐 在 2,4-双(4-苯氧苯基)-1,3-二硫杂-2,4-二磷杂环丁烷-2,4-二硫化物 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 57.0h， 生成 (S)-ethyl 2-(1-(tert-butoxycarbonylamino)-2-phenylethyl)thiazole-4-carboxylate
  参考文献：
  名称：

  A convenient method for the preparation of 2-(1-aminoalkyl)thiazole-4-carboxylic acids, key intermediates in the total synthesis of naturally occurring antitumor cyclopeptides

  摘要：

  DOI：

  10.1021/jo00215a040

文献信息

• Oxidation of Oxazolines and Thiazolines to Oxazoles and Thiazoles. Application of the Kharasch−Sosnovsky Reaction
  作者：A. I. Meyers、Francis X. Tavares

  DOI：10.1021/jo9613491

  日期：1996.11.15

  Kharasch-Sosnovsky reaction, the oxidation of oxazolines and thiazolines bearing a variety of 2-alkyl substituents (chiral and achiral) were smoothly oxidized to their corresponding oxazoles and thiazoles, respectively. The key feature involved in the successful implementation of this important oxidation was the use of a mixture of Cu(I) and Cu(II) salts to enhance the oxidation of the intermediate captodative

  使用Kharasch-Sosnovsky反应的改进，将带有各种2-烷基取代基（手性和非手性）的恶唑啉和噻唑啉的氧化分别平滑地氧化为相应的恶唑和噻唑。成功实施此重要氧化反应的关键特征是使用Cu（I）和Cu（II）盐的混合物来增强中间俘虏性自由基的氧化作用24。氧化失败的原因是在C-4处缺少碳烷氧基的恶唑啉/噻唑啉。
• Thiazole–Carbonyl Interactions: A Case Study Using Phenylalanine Thiazole Cyclic Tripeptides
  作者：Sachitanand M. Mali、Tobias F. Schneider、Anupam Bandyopadhyay、Sandip V. Jadhav、Daniel B. Werz、Hosahudya N. Gopi

  DOI：10.1021/cg301147s

  日期：2012.11.7

  observed. S···O interactions between the sulfur of a thiazole ring and a carbonyl moiety of an amide showing an average distance of 3.1 Å which is much smaller than the sum of the van der Waals radii predominantly mediate the crystal structure. To get deeper insights into this kind of interaction, two model systems consisting of thiazole and acetyl-N-methylamide were studied using the MP2/6-311G++(3df,3dp)

  天然以及合成的噻唑/恶唑肽均已显示出广泛的药理和金属结合特性。在此，合成了苯丙氨酸和酪氨酸衍生的含噻唑的环状三肽，并研究了溶剂对固态超分子组装的影响。观察到溶剂对固态结构的显着影响。噻唑环的硫与酰胺的羰基部分之间的S·O相互作用显示出3.1的平均距离，该距离远小于范德华半径的总和，主要介导了晶体结构。为了更深入地了解这种相互作用，建立了由噻唑和乙酰基-N组成的两个模型系统使用MP2 / 6-311G ++（3df，3dp）的理论水平研究了-甲酰胺。理论计算表明，与分离的物种相比，这些相互作用与约16 kJ / mol的平均能量增益相关。
• RITA Mimics: Synthesis and Mechanistic Evaluation of Asymmetric Linked Trithiazoles
  作者：Adrian L. Pietkiewicz、Yuqi Zhang、Marwa N. Rahimi、Michael Stramandinoli、Matthew Teusner、Shelli R. McAlpine

  DOI：10.1021/acsmedchemlett.6b00488

  日期：2017.4.13

  The established cytotoxic agent RITA contains a thiophene-furan-thiophene backbone and two terminal alcohol groups. Herein we investigate the effect of using thiazoles as the backbone in RITA-like molecules and modifying the terminal groups of these trithiazoles, thereby generating 41 unique structures. Incorporating side chains with varied steric bulk allowed us to investigate how size and a stereocenter impacted biological activity. Subjecting compounds to growth inhibition assays on HCT-116 cells showed that the most potent compounds 7d, 7e, and 7h had GI₅₀ values of 4.4, 4.4, and 3.4 μM, respectively, versus RITA (GI₅₀ of 800 nM). Analysis of these compounds in apoptosis assays proved that 7d, 7e, and 7h were as effective as RITA at inducing apoptosis. Evaluating the impact of 7h on proteins targeted by RITA (p53, c-Myc, and Mcl-1) indicated that it acts via a different mechanism of action to that of RITA. RITA suppressed Mcl-1 protein via p53, whereas compound 7h suppressed Mcl-1 expression via an alternative mechanism independent of p53.
• 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 and antiproliferative activity of a cyclic analog of dolastatin 10
  作者：Joël Poncet、Laurent Hortala、Magali Busquet、Françoise Guéritte-Voegelein、Sylvie Thoret、Alain Pierré、Ghanem Atassi、Patrick Jouin

  DOI：10.1016/s0960-894x(98)00511-3

  日期：1998.10

  A cyclic analog of the natural antiproliferative compound dolastatin 10 was synthesized by introducing an ester link between the N- and C-terminal residues which were modified accordingly. The final macrolactonization was performed by using isopropenyl chloroformate and DMAP as reagents. This analog exhibits submicromolar antiproliferative activity against the L1210 and HT29 cell lines and inhibits in vitro tubulin polymerization (IC50, 39 mu M). (C) 1998 Elsevier Science Ltd. All lights reserved.