ethyl [(2Z,3R)-3-(1-hydroxyethyl)-4-oxoazetidin-2-ylidene]acetate | 410524-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: ethyl [(2Z,3R)-3-(1-hydroxyethyl)-4-oxoazetidin-2-ylidene]acetate
• 英文别名: ethyl (2Z)-2-[(3S)-3-[(1R)-1-hydroxyethyl]-4-oxoazetidin-2-ylidene]acetate
• CAS: 410524-30-0
• 化学式: C₉H₁₃NO₄
• 分子量: 199.207
• InChiKey: GXTOIRLOCMMMBC-PILZFTNBSA-N

物化性质

• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl [(2Z,3R)-3-(1-hydroxyethyl)-4-oxoazetidin-2-ylidene]acetate 在 palladium on activated charcoal 氢气 、 四氯化锡 作用下， 以 四氢呋喃 、 甲醇 、 苯 为溶剂， 反应 8.0h， 生成 3,5-Dihydroxy-benzoic acid (R)-1-{(S)-2-[1-ethoxycarbonyl-meth-(Z)-ylidene]-4-oxo-azetidin-3-yl}-ethyl ester
  参考文献：
  名称：

  4-Alkyliden-β-lactams conjugated to polyphenols: Synthesis and inhibitory activity

  摘要：

  A series of compounds combining the beta-lactain and polyphenol scaffold have been prepared and evaluated for inhibition of human leukocyte elastase and matrix metallo-proteases MMP-2 and MMP-9. The design of these compounds has been based on the 'overlapping-type' strategy where two pharmacophores are linked in a single molecule. The most powerful compound against elastase was an N-galloyl-4-alkyliden beta-lactam, [3-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-1-(3,4,5-tris-benzyloxy-benzoyl)-azetidin-2-ylidene]-acetic acid ethylester, with an IC50 of 0.5 mu M; while the most powerful against MMP-2 was a 4-alkyliden beta-lactam arylated on the C-3 hydroxy side chain (3,5-bis-benzyloxy-4-hydroxy-benzoic acid 1-(2-benzyloxycarbonylmethylene4-oxo-azetidin-3-yl)-ethyl ester) with an IC50 of 4 mu M. Of the total 35 compounds tested, high levels of inhibition of elastase and of MMPs were separately exerted by distinct molecules. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.041
• 作为产物：
  描述：

  ethyl {(2E,3S)-3-[(1R)-(tert-butyldimethylsilanyloxy)ethyl]-4-oxoazetidin-2-ylidene}acetate 在 盐酸 作用下， 以 乙腈 为溶剂， 生成 ethyl [(2Z,3R)-3-(1-hydroxyethyl)-4-oxoazetidin-2-ylidene]acetate
  参考文献：
  名称：

  4-Alkyliden-β-lactams conjugated to polyphenols: Synthesis and inhibitory activity

  摘要：

  A series of compounds combining the beta-lactain and polyphenol scaffold have been prepared and evaluated for inhibition of human leukocyte elastase and matrix metallo-proteases MMP-2 and MMP-9. The design of these compounds has been based on the 'overlapping-type' strategy where two pharmacophores are linked in a single molecule. The most powerful compound against elastase was an N-galloyl-4-alkyliden beta-lactam, [3-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-1-(3,4,5-tris-benzyloxy-benzoyl)-azetidin-2-ylidene]-acetic acid ethylester, with an IC50 of 0.5 mu M; while the most powerful against MMP-2 was a 4-alkyliden beta-lactam arylated on the C-3 hydroxy side chain (3,5-bis-benzyloxy-4-hydroxy-benzoic acid 1-(2-benzyloxycarbonylmethylene4-oxo-azetidin-3-yl)-ethyl ester) with an IC50 of 4 mu M. Of the total 35 compounds tested, high levels of inhibition of elastase and of MMPs were separately exerted by distinct molecules. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.041

文献信息

• Design, Synthesis, and Biological Evaluation of 4-Alkyliden-beta Lactams:  New Products with Promising Antibiotic Activity Against Resistant Bacteria
  作者：Francesco Broccolo、Gianfranco Cainelli、Gianluigi Caltabiano、Clementina E. A. Cocuzza、Cosimo G. Fortuna、Paola Galletti、Daria Giacomini、Giuseppe Musumarra、Rosario Musumeci、Arianna Quintavalla

  DOI：10.1021/jm0580510

  日期：2006.5.1

  The design, synthesis, and antibacterial activity of 4-alkyliden-azetidin-2-ones as new antimicrobial agents against multidrug-resistant pathogens is reported. 4-Alkyliden-azetidin-2-ones were easily obtained using an original protocol starting from 4-acetoxy-azetidinones and diazoesters. Parent compounds were further elaborated to obtain a small library of 4-alkylidene derivatives. A molecular modeling

  据报道4-亚烷基-氮杂环丁烷-2-酮作为新型抗多药耐药病原体的抗菌剂的设计，合成和抗菌活性。从4-乙酰氧基-氮杂环丁烷酮和重氮酯开始，可以使用原始方案轻松获得4-炔基-氮杂环丁烷-2-酮。进一步详细阐述了母体化合物，以获得一个小型的4-亚烷基衍生物库。使用基于VRS概念的GRID描述符的分子建模方法可识别出有吸引力的药物候选物，并有助于QSAR中官能团效应的合理化。通过确定其最低抑菌浓度（MIC），评估了新药对43种近期对抗生素敏感和耐药的革兰氏阳性和革兰氏阴性病原体临床分离株的体外抗菌活性。活性最高的化合物对某些测试细菌的MIC值为0.25至32 mg / L。有趣的是，一些化合物对金黄色葡萄球菌对甲氧西林敏感和耐药的菌株表现出相似的活性，表明这些试剂的可能替代作用机制是由细胞毒性和初步扫描电子显微镜研究支持的。
• Synthesis of Novel 4-(2-Oxoethylidene)azetidin-2-ones by a Lewis Acid Mediated Reaction of Acyldiazo Compounds
  作者：Gianfranco Cainelli、Daria Giacomini、Paola Galletti、Arianna Quintavalla

  DOI：10.1002/ejoc.200210702

  日期：2003.5

  on the nature of the C-3 side chain, the Lewis acid, and the β-lactam protection. VT NMR spectroscopic experiments and X-ray structural analysis of crystalline derivatives demonstrate the presence of an intramolecular hydrogen bond in Z isomers, which drives the stereochemical outcome of the reaction. A possible mechanism for this novel reaction is proposed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451

  我们报告了通过酰基重氮化合物与 4-乙酰氧基氮杂环丁烷-2-ones 的新型路易斯酸介导反应合成一类 4-(2-oxoethylidene) azetidin-2-ones。使用这种方法，根据起始氮杂环丁酮和 α-重氮羰基化合物的选择，获得了 C-3-和 C-4-取代的 4-亚烷基氮杂环丁烷-2-酮。该产品显示了 C-4 双键的出色 Z 非对映选择。根据 C-3 侧链、路易斯酸和 β-内酰胺保护的性质，可以获得不同数量的 E 异构体。晶体衍生物的 VT NMR 光谱实验和 X 射线结构分析表明，Z 异构体中存在分子内氢键，这推动了反应的立体化学结果。提出了这种新反应的可能机制。(© Wiley-VCH Verlag GmbH & Co.
• Synthesis of novel 4-(1-ethoxycarbonyl-methylidene)-azetidin-2-ones via a Lewis acid-catalyzed reaction of ethyl diazoacetate
  作者：Gianfranco Cainelli、Paola Galletti、Massimo Gazzano、Daria Giacomini、Arianna Quintavalla

  DOI：10.1016/s0040-4039(01)02108-6

  日期：2002.1

  Treatment of (3R,4R,1′R)-3-[1-(t-butyldimethylsilyloxy)ethyl]-4-acetoxy-azetidin-2-one with ethyl diazoacetate in the presence of a Lewis acid such as TiCl4, TiF4, AlCl3 or SnCl4 affords the novel (3S,1′R)-3-[1-(t-butyldimethylsilyloxy)ethyl]-4(1-ethoxycarbonyl-methylidene)-azetidin-2-one as an E and/or Z isomer.

  （3治疗- [R，4 - [R，1' - [R）-3- [1-（吨-butyldimethylsilyloxy）乙基] -4-乙酰氧基-氮杂环丁烷-2-酮与重氮基乙酸乙酯在路易斯酸如的存在的TiCl 4，TIF 4，的AlCl 3或的SnCl 4次，得到新颖（3小号，1' - [R）-3- [1-（吨-butyldimethylsilyloxy）乙基] -4-（1-乙氧羰基亚甲基） -氮杂环丁-2-酮，为E和/或Z异构体。
• Synthesis of the Mannopeptimycin Disaccharide and Its Conjugation with 4-Alkylidene-β-lactams
  作者：Matteo Adinolfi、Daria Giacomini、Alfonso Iadonisi、Arianna Quintavalla、Silvia Valerio

  DOI：10.1002/ejoc.200701159

  日期：2008.6

  The disaccharide moiety of the antibiotic mannopeptimycin has been synthesized as a (N-phenyl)trifluoroacetimidate donor, the reactivity of which was tested in conjugation with a 4-alkylidene-β-lactam acceptor. Key steps of the synthesis were Bi(OTf)3-catalyzed glycosidations that proceeded in short times and with high yields and stereocontrol. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany

  抗生素甘露肽霉素的二糖部分已合成为（N-苯基）三氟乙酰亚胺供体，其反应性在与 4-亚烷基-β-内酰胺受体结合时进行了测试。合成的关键步骤是 Bi(OTf)3 催化的糖苷化，其在短时间内以高产率和立体控制进行。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
• Toward Novel Glyconjugates: Efficient Synthesis of Glycosylated 4-Alkylidene--lactams
  作者：Matteo Adinolfi、Paola Galletti、Daria Giacomini、Alfonso Iadonisi、Arianna Quintavalla、Alessandra Ravidà

  DOI：10.1002/ejoc.200500665

  日期：2006.1

  A new class of glycoconjugated β-lactams was accessed by direct glycosidation of a suitable 4-alkylidene-azetidin-2-one acceptor with several perbenzylated (N-phenyl)trifluoroacetimidate donors activated by catalytic Yb(OTf)3. Goodstereocontrol was achieved by relying on the stereo directing effect of nitrile or ether solvents. Transfer hydrogenolysis under carefully controlled conditions enabled the

  通过将合适的 4-亚烷基-氮杂环丁烷-2-one 受体与几个由催化 Yb(OTf)3 活化的过苄基化 (N-苯基) 三氟乙酰亚胺供体直接糖苷化，获得了一类新的糖偶联 β-内酰胺。良好的立体控制是依靠腈或醚溶剂的立体定向作用实现的。在严格控制的条件下进行转移氢解，可以在不影响 β-内酰胺双键的情况下去除苄基。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)