(R,S)-methyl 3-methyl-2-{[(2E)-3-phenylprop-2-enoyl]amino}butanoate | 127750-57-6

• 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: (R,S)-methyl 3-methyl-2-{[(2E)-3-phenylprop-2-enoyl]amino}butanoate
• 英文别名: N-cinnamoyl-D,L-valine methyl ester；methyl 3-methyl-2-[[(E)-3-phenylprop-2-enoyl]amino]butanoate
• CAS: 127750-57-6
• 化学式: C₁₅H₁₉NO₃
• mdl: MFCD00706831
• 分子量: 261.321
• InChiKey: FPCRRVNOCVWNIW-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R,S)-methyl 3-methyl-2-{[(2E)-3-phenylprop-2-enoyl]amino}butanoate 在 氢溴酸 、 双氧水 作用下， 以 乙醇 为溶剂， 反应 0.58h， 生成 methyl N-(α, β-dibromo-β-phenylpropanoyl)valinate 、 methyl N-(α, β-dibromo-β-phenylpropanoyl)valinate
  参考文献：
  名称：

  N-肉桂酰氨基酸酰胺的超声辅助绿色溴化——结构表征和抗菌评价

  摘要：

  摘要 N-苯基丙烯酰基氨基酸酰胺已使用两种替代的声化学活化绿色化学程序进行溴化。第一个合成过程涉及在水性介质中使用离子液体作为反应催化剂的超声辅助溴化，而在第二个合成过程中，已经使用通过 H 2 O 2 氧化 HBr 原位形成 Br 2 。为了比较，还使用了传统的溴化程序。新溴化的化合物通过适当的分析技术进行表征。使用密度泛函理论 (DFT) 方法进行的详细 NMR 光谱分析和量子化学计算已用于定义产品的立体化学。结果证实了通过所采用的三种合成程序获得的产物的物理化学特性和相似的产率，并揭示了新合成产物的两种非对映异构形式的共存。评价了二溴化酰胺的抗菌和抗真菌活性。

  DOI：

  10.1016/j.molstruc.2017.01.056
• 作为产物：
  描述：

  DL-缬氨酸甲酯盐酸盐 、 3-苯基-2-丙烯酰氯 在 potassium carbonate 作用下， 以 水 、 甲苯 为溶剂， 反应 0.33h， 以86%的产率得到(R,S)-methyl 3-methyl-2-{[(2E)-3-phenylprop-2-enoyl]amino}butanoate
  参考文献：
  名称：

  Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols

  摘要：

  Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock - MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as R-M0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 angstrom - from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 angstrom - from the phenyl ring to the amide group, and 3.112 angstrom - from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.051

文献信息

• Anti-Helicobacter pylori activities of selected N-substituted cinnamamide derivatives evaluated on reference and clinical bacterial strains
  作者：Karolina Klesiewicz、Elżbieta Karczewska、Paweł Nowak、Iwona Skiba-Kurek、Edward Sito、Katarzyna Pańczyk、Paulina Koczurkiewicz、Dorota Żelaszczyk、Elżbieta Pękala、Anna M. Waszkielewicz、Alicja Budak、Henryk Marona、Agnieszka Gunia-Krzyżak

  DOI：10.1038/s41429-018-0027-1

  日期：2018.5

  In this study, thirty-five N-substituted derivatives of cinnamic acid amide (cinnamamide) were evaluated for anti-Helicobacter pylori activity using an agar disc-diffusion method. Qualitative screening was performed on a reference H. pylori strain (ATCC 43504), resulting in the identification of the three most active compounds, 8 (R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide, minimal inhibitory concentration, MIC = 7.5 µg/mL), 23 ((2E)-3-(4-chlorophenyl)-N-(2-hydroxycyclohexyl)prop-2-enamide, MIC = 10 µg/mL), and 28 ((2E)-3-(4-chlorophenyl)-N-(4-oxocyclohexyl)prop-2-enamide, MIC = 10 µg/mL). These compounds were further tested on twelve well-characterized clinical strains, yielding MIC values that ranged from 10 to 1000 µg/mL. Preliminary safety assessments of the compounds were made using the MTT viability test for cytotoxicity and Ames test for mutagenicity, which showed them to be generally safe, although compounds 8 and 28 showed mutagenic activity at some of the tested concentrations. The results of this study showed the anti-H. pylori potential of cinnamamide derivatives.

  在本项研究中，使用琼脂平板扩散法对三十五种N-取代肉桂酸酰胺（肉桂酰胺）衍生物进行了抗幽门螺杆菌活性评估。通过对参考幽门螺杆菌菌株（ATCC 43504）的定性筛选，鉴定出三种最具活性的化合物，分别为8号（R,S-(2E)-3-(4-氯苯基)-N-(2-羟丙基)丙-2-烯酰胺，最小抑制浓度MIC=7.5μg/mL）、23号（(2E)-3-(4-氯苯基)-N-(2-羟环己基)丙-2-烯酰胺，MIC=10μg/mL）和28号（(2E)-3-(4-氯苯基)-N-(4-氧环己基)丙-2-烯酰胺，MIC=10μg/mL）。随后，这些化合物在十二种特征明确的临床菌株上进行了进一步测试，得到的MIC值范围从10到1000μg/mL不等。通过MTT活力度测试评估细胞毒性和Ames试验评估诱变性，对这些化合物进行了初步安全性评估，结果显示它们总体上是安全的，尽管在某些测试浓度下，8号和28号化合物表现出诱变活性。本研究结果表明，肉桂酰胺衍生物具有抗幽门螺杆菌的潜力。
• Synthesis of pseudosparsomycins
  作者：A. A. Arutyunyan、R. G. Melik-Ogadzhanyan、L. G. Alaverdova、S. A. Papoyan、Yu. Z. Ter-Zakharyan、É. V. Kazaryan、G. M. Paronikyan、T. P. Sarkisyan

  DOI：10.1007/bf00764814

  日期：1989.10
• ARUTYUNYAN, A. A.;MELIK-OGADZHANYAN, R. G.;ALAVERDOVA, L. G.;PAPOYAN, S. +, XIM.-FARMATS. ZH., 23,(1989) N0, S. 1223-1226
  作者：ARUTYUNYAN, A. A.、MELIK-OGADZHANYAN, R. G.、ALAVERDOVA, L. G.、PAPOYAN, S. +

  DOI：——

  日期：——
• Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols
  作者：Agnieszka Gunia-Krzyżak、Ewa Żesławska、Karolina Słoczyńska、Paulina Koczurkiewicz、Wojciech Nitek、Dorota Żelaszczyk、Natalia Szkaradek、Anna M. Waszkielewicz、Elżbieta Pękala、Henryk Marona

  DOI：10.1016/j.ejmech.2015.10.051

  日期：2016.1

  Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock - MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as R-M0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 angstrom - from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 angstrom - from the phenyl ring to the amide group, and 3.112 angstrom - from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2). (C) 2015 Elsevier Masson SAS. All rights reserved.
• Ultrasound-assisted green bromination of N-cinnamoyl amino acid amides – Structural characterization and antimicrobial evaluation
  作者：Boyka Stoykova、Maya Chochkova、Galya Ivanova、Nadezhda Markova、Venelin Enchev、Iva Tsvetkova、Hristo Najdenski、Martin Štícha、Tsenka Milkova

  DOI：10.1016/j.molstruc.2017.01.056

  日期：2017.5

  Abstract N -phenylpropenoyl amino acid amides have been brominated using two alternative sonochemically activated green chemistry procedures. The first synthetic procedure has involved an ultrasound assisted bromination in an aqueous medium using ionic liquid as a catalyst of the reaction, whereas in the second one an in situ formation of Br 2 via oxidation of HBr by H 2 O 2 has been used. For comparison

  摘要 N-苯基丙烯酰基氨基酸酰胺已使用两种替代的声化学活化绿色化学程序进行溴化。第一个合成过程涉及在水性介质中使用离子液体作为反应催化剂的超声辅助溴化，而在第二个合成过程中，已经使用通过 H 2 O 2 氧化 HBr 原位形成 Br 2 。为了比较，还使用了传统的溴化程序。新溴化的化合物通过适当的分析技术进行表征。使用密度泛函理论 (DFT) 方法进行的详细 NMR 光谱分析和量子化学计算已用于定义产品的立体化学。结果证实了通过所采用的三种合成程序获得的产物的物理化学特性和相似的产率，并揭示了新合成产物的两种非对映异构形式的共存。评价了二溴化酰胺的抗菌和抗真菌活性。