(4R)-2-benzyl-4,5-dihydrothiazole-4-carboxylic acid methyl ester | 341027-48-3

• 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: (4R)-2-benzyl-4,5-dihydrothiazole-4-carboxylic acid methyl ester
• 英文别名: methyl (4R)-2-benzyl-4,5-dihydro-1,3-thiazole-4-carboxylate
• CAS: 341027-48-3
• 化学式: C₁₂H₁₃NO₂S
• 分子量: 235.307
• InChiKey: QZYVYPFMHLQSPP-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R)-2-benzyl-4,5-dihydrothiazole-4-carboxylic acid methyl ester 在 盐酸 、 lithium hydroxide 、 Amberlite IR-120 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 0.05h， 生成 (3R)-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid
  参考文献：
  名称：

  Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Aβ-peptide aggregation inhibitors

  摘要：

  开发了一种无试剂的微波辅助去羧化程序，用于羧酸功能化的双环2-吡啶酮。该新方法基于在N-甲基吡咯烷酮（NMP）中以220°C加热600秒，证明实用且非常高效，产生的去羧化2-吡啶酮几乎定量。去羧化产品和羧酸甲酯及羧酸形式的中间体2-吡啶酮被筛选以研究其对Aβ肽聚集的影响。在本研究中描述的21种2-吡啶酮中，有两种抑制了阿尔茨海默病Aβ(1–40)肽的淀粉样蛋白形成。即使在2-吡啶酮与单体Aβ肽的比率为4:1时，仍观察到了这种效果。

  DOI：

  10.1039/b503294f
• 作为产物：
  描述：

  L-半胱氨酸甲酯盐酸盐 、 ethyl 2-phenylacetimidate hydrochloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (4R)-2-benzyl-4,5-dihydrothiazole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure–activity study

  摘要：

  Pilicides prevent pili formation and thereby the development of bacterial biofilms in Escherichia coli. We have performed a comprehensive structure activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone pilicide central fragment by varying all open positions. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to distinguish active from inactive compounds in which polarity proved to be the most important factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS) model was calculated on the active compounds for prediction of biofilm inhibition activity. In this model, compounds with high inhibitory activity were generally larger, more lipophilic, more flexible and had a lower HOMO. Overall, this resulted in both highly valuable SAR information and potent inhibitors of type 1 pili dependent biofilm formation. The most potent biofilm inhibitor had an EC50 of 400 nM. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.01.048

文献信息

• Design and Synthesis of Fluorescent Pilicides and Curlicides: Bioactive Tools to Study Bacterial Virulence Mechanisms
  作者：Erik Chorell-、Jerome S. Pinkner、Christoffer Bengtsson、Sofie Edvinsson、Corinne K. Cusumano、Erik Rosenbaum、Lennart B. Å. Johansson、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1002/chem.201103936

  日期：2012.4.10

  Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure–activity knowledge, in which key pilicide and curlicide substituents

  Pilicides 和 curlicides 是分别阻止毒力因子 pili 和 curli 形成的化合物。为了促进对这些化合物与菌毛和卷曲组装系统之间相互作用的研究，已经合成了荧光 pilicides 和 curlicides。这是通过使用基于结构-活性知识的策略来实现的，其中环稠合二氢噻唑并 2-吡啶酮中心片段上的关键 pilicide 和 curlicide 取代基被荧光团取代。在依赖菌毛和卷曲的生物膜测定中测量到的几种荧光化合物的活性有所提高。我们通过引入香豆素和 4,4-difluoro-4-bora-3a,4a-diaza- s创建了荧光 pilicides 和 curlicides- 茚(BODIPY) 荧光团位于拟肽 pilicide 和 curlicide 中心片段的两个位置。在这些化合物存在下生长的尿路致病性大肠杆菌(UPEC) 菌株 UTI89 的荧光图像表明，这些化合物与具有异质分布的细菌密切相关。
• Synthesis of a Novel Tricyclic Peptidomimetic Scaffold
  作者：Magnus Sellstedt、Fredrik Almqvist

  DOI：10.1021/ol801506y

  日期：2008.9.18

  An efficient method to synthesize a novel rigid tricyclic peptidomimetic scaffold through ring-closure of amino-functionalized bicyclic 2-pyridones has been discovered. The scaffold can function as a peptide backbone mimetic (highlighted) with two substituents independently variable to fine-tune biological response. Halogenation of the pyrazolo ring followed by Suzuki couplings made it possible to

  已发现通过氨基官能化的双环2-吡啶酮的闭环合成新型刚性三环拟肽骨架的有效方法。支架可以用作具有两个独立取代基的肽骨架模拟物（突出显示），以微调生物学反应。吡唑并环的卤化和随后的铃木偶联使在合成路线的后期引入具有可变电子性质的取代基成为可能，这在文库合成中是优选的。
• Synthesis and Characterization of a Multi Ring-Fused 2-Pyridone-Based Fluorescent Scaffold
  作者：Magnus Sellstedt、Anders Nyberg、Erik Rosenbaum、Patrik Engström、Malin Wickström、Joachim Gullbo、Sven Bergström、Lennart B.-Å. Johansson、Fredrik Almqvist

  DOI：10.1002/ejoc.201000796

  日期：2010.11

  A series of compounds based on a novel fluorescent scaffold have been synthesized. Most of the compounds displayed high quantum yields of fluorescence and unusually long fluorescence lifetimes. HeLa cells were treated with one of the compounds and its use as a fluorescent dye was demonstrated with fluorescence confocal microscopy.

  已经合成了一系列基于新型荧光支架的化合物。大多数化合物显示出高荧光量子产率和异常长的荧光寿命。HeLa 细胞用其中一种化合物处理，荧光共聚焦显微镜证明了其作为荧光染料的用途。
• K₂S₂O₈-mediated coupling of 6-amino-7-aminomethyl-thiazolino-pyridones with aldehydes to construct amyloid affecting pyrimidine-fused thiazolino-2-pyridones
  作者：Jaideep B. Bharate、Jörgen Ådén、Anna Gharibyan、Dan E. Adolfsson、Sanduni Wasana Jayaweera、Pardeep Singh、Katarina Vielfort、Mohit Tyagi、Mari Bonde、Sven Bergström、Anders Olofsson、Fredrik Almqvist

  DOI：10.1039/d1ob01580j

  日期：——

  We herein present the synthesis of diversely functionalized pyrimidine fused thiazolino-2-pyridones via K₂S₂O₈-mediated oxidative coupling of 6-amino-7-(aminomethyl)-thiazolino-2-pyridones with aldehydes.

  我们在此提出了通过K₂S₂O₈介导的氧化偶联，合成了多样化官能化的嘧啶融合噻唑-2-吡啶酮，该噻唑-2-吡啶酮与醛类发生反应。
• An Enantioselective Ketene−Imine Cycloaddition Method for Synthesis of Substituted Ring-Fused 2-Pyridinones
  作者：Hans Emtenäs、Lisa Alderin、Fredrik Almqvist

  DOI：10.1021/jo015794u

  日期：2001.10.1

  Previously, a method for the stereoselective synthesis of P-lactams, starting from 2H-Delta (2)-thiazolines and Meldrum's acid derivatives, has been reported from our laboratory. We now report a new method for the synthesis of optically active, highly substituted ring-fused 2-pyridinones. This was discovered when 2-alkyl-Delta (2)-thiazolines and Meldrum's acid derivatives were treated with HCl(g) in benzene at 5 --> 78 degreesC. Further refinement of the synthetic protocol revealed that use of 1,2-dichloroethane as solvent at 0 --> 64 degreesC led to the desired 2-pyridinones;in good yields and with excellent enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones from several different Delta (2)-thiazolines and Meldrum's acid derivatives and may be a general route to 2-pyridinones.