2,5-dioxopyrrolidin-1-yl (E)-3-(3,4-dimethoxyphenyl)acrylate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2,5-dioxopyrrolidin-1-yl (E)-3-(3,4-dimethoxyphenyl)acrylate
• 英文别名: (e)-2,5-Dioxopyrrolidin-1-yl 3-(3,4-dimethoxyphenyl)acrylate；(2,5-dioxopyrrolidin-1-yl) (E)-3-(3,4-dimethoxyphenyl)prop-2-enoate
• 化学式: C₁₅H₁₅NO₆
• 分子量: 305.287
• InChiKey: IQTAMSBUOWDMLM-XBXARRHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidin-1-yl (E)-3-(3,4-dimethoxyphenyl)acrylate 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 生成 3-(3,4-Dimethoxy-phenyl)-N-[3-(4-{3-[3-(3,4-dimethoxy-phenyl)-propionylamino]-propylamino}-butylamino)-propyl]-propionamide; compound with GENERIC INORGANIC NEUTRAL COMPONENT
  参考文献：
  名称：

  Very Short and Efficient Syntheses of the Spermine Alkaloid Kukoamine A and Analogs Using Isolable Succinimidyl Cinnamates

  摘要：

  摘要 用多种可分离的琥珀酰亚胺基肉桂酸酯对精胺和亚精胺的初级氨基功能进行直接选择性酰化，然后进行催化氢化反应，可获得高产率的精胺生物碱 Kukoamine A 和适合结构-活性关系研究的类似物。通过芳香醛与酰化物 Ph3P=CRCO2Me 的 Wittig 反应，然后在 N,N′-二环己基碳二亚胺存在下用 N-hydroxysuccinimide 进行皂化和活化，很容易获得合适的琥珀酰亚胺肉桂酸盐。

  DOI：

  10.1246/cl.2005.264
• 作为产物：
  描述：

  methyl (E)-3-(3,4-dimethoxyphenyl)acrylate 在 sodium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 2,5-dioxopyrrolidin-1-yl (E)-3-(3,4-dimethoxyphenyl)acrylate
  参考文献：
  名称：

  Very Short and Efficient Syntheses of the Spermine Alkaloid Kukoamine A and Analogs Using Isolable Succinimidyl Cinnamates

  摘要：

  摘要 用多种可分离的琥珀酰亚胺基肉桂酸酯对精胺和亚精胺的初级氨基功能进行直接选择性酰化，然后进行催化氢化反应，可获得高产率的精胺生物碱 Kukoamine A 和适合结构-活性关系研究的类似物。通过芳香醛与酰化物 Ph3P=CRCO2Me 的 Wittig 反应，然后在 N,N′-二环己基碳二亚胺存在下用 N-hydroxysuccinimide 进行皂化和活化，很容易获得合适的琥珀酰亚胺肉桂酸盐。

  DOI：

  10.1246/cl.2005.264

文献信息

• A Convenient Synthesis of Bis-(dihydro)caffeoylspermidines
  作者：Lili He、Jian Sun、Pengjuan Zhou、Jingwen Ji、Lijuan Zhai、Dong Tang、Jinbo Ji、Haikang Yang、Zafar Iqbal、Zhixiang Yang

  DOI：10.2174/0115701786265776230929180406

  日期：2024.4

  bisdihydrocaffeoylspermidine using cheaper and commercially available starting materials in 97% and 86% overall yields, respectively. The synthetic scheme can be upgraded to the commercial-scale synthesis of these compounds.

  咖啡酰亚精胺是许多植物物种中天然存在的有价值的生物碱。这些生物碱是传统药物中使用的许多植物提取物的药理学重要成分。双咖啡酰亚精胺和双二氢咖啡酰亚精胺具有抗氧化、抗炎和酶抑制特性，使其成为更安全的治疗剂的宝贵天然来源。然而，这些化合物在自然界中的可用性有限引起了合成化学家的关注。因此，我们使用更便宜且市售的起始原料合成了双咖啡酰亚精胺和双二氢咖啡酰亚精胺，总产率分别为 97% 和 86%。该合成方案可以升级为这些化合物的商业规模合成。
• 10.1007/s10600-024-04409-0
  作者：Zhai, Lijuan、Sun, Jian、Zhou, Pengjuan、Ji, Jingwen、He, Lili、Tang, Dong、Ji, Jinbo、Yang, Haikang、Iqbal, Zafar、Yang, Zhixiang

  DOI：10.1007/s10600-024-04409-0

  日期：——

  plant extract from Lycium root, bark, and fruit. The recent pharmacological significance of this alkaloid makes it a potential therapeutic target for the pharmaceutical industry. We accomplished the synthesis of kukoamine A in a 73% yield over four steps starting from cheaper commercial reagents, ambient reaction conditions, and minimal purification efforts.

  几十年来，Kukoamine A 一直被认为是从枸杞根、树皮和果实中提取的中药植物提取物的抗炎和降血压成分。这种生物碱最近的药理学意义使其成为制药行业的潜在治疗靶点。我们从更便宜的商业试剂、环境反应条件和最少的纯化工作出发，通过四个步骤完成了 kukoamine A 的合成，产率达到 73%。
• Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N.epsilon.)-amide residues
  作者：Kazumi Shiosaki、Chun Wel Lin、Hana Kopecka、Richard A. Craig、Bruce R. Bianchi、Thomas R. Miller、David G. Witte、Michael Stashko、Alex M. Nadzan

  DOI：10.1021/jm00089a010

  日期：1992.5

  A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp-Lys(N(epsilon)-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or aliphatic group, are potent and selective CCK-AT receptor agonists. These amide-bearing compounds complement the previously described urea-based tetrapeptides (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842); structure-activity studies revealed parallel as well as divergent trends between these two series. A significant correlation was observed between pancreatic binding affinity and the resonance constant R of the phenyl substituent in one particular series of derivatives. Sulfation of phenolic amides appended onto the epsilon-amino group of the lysine did not affect affinity for the CCK-AT receptor in contrast to the 500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural elements that impart high affinity for the CCK-A receptor, are interacting differently with the receptor. The amide-bearing tetrapeptides are full agonists relative to CCK-8 in stimulating pancreatic amylase release while being partial agonists in eliciting phosphoinositide (PI) hydrolysis. Both effects were blocked by selective CCK-A receptor antagonists.
• Does conjugation of antioxidants improve their antioxidative/anti-inflammatory potential?
  作者：Dimitra Hadjipavlou-Litina、George E. Magoulas、Stavros E. Bariamis、Denis Drainas、Konstantinos Avgoustakis、Dionissios Papaioannou

  DOI：10.1016/j.bmc.2010.10.012

  日期：2010.12

  A series of symmetric and asymmetric spermine (SPM) conjugates with all-trans-retinoic acid (ATRA), acitretin (ACI), (E)-3-(trioxsalen-4'-yl)acrylic acid (TRAA) and L-DOPA, amides of ACI, L-DOPA and TRAA with 1-aminobutane, benzylamine, dopamine and 1,12-diaminobutane as well as hybrid conjugates of O,O'-dimethylcaffeic acid (DMCA) with TRAA or N-fumaroyl-indole-3-carboxanilide (FICA) and 2-(2-aminoethoxy) ethanol were synthesized and their antioxidant properties were studied. The reducing activity (RA)% of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay and found to be in the range 0-92(20 min)%/96(60 min)% at 100 mu M, the most powerful being the conjugates L-DOPA-SPM-L-DOPA (8, RA = 89%/96%) and L-DOPA-dopamine (13, RA = 92%/92%). Conjugate DMCA-NH(CH2CH2O)(2)-FICA (14) was the most powerful LOX inhibitor with IC50 33.5 mu M, followed by the conjugates ACI-NHCH2Ph (10, IC50 40.5 mu M), ACI-SPM-TRAA (7, IC50 41.5 mu M), DMCA-NH(CH2CH2O)(2)-TRAA (15, IC50 65 mu M), 13 (IC50 81.5 mu M) and ACI-dopamine (11, IC50 87 mu M). The most potent inhibitors of lipid peroxidation at 100 mu M were the conjugates 15 (98%) and ACI-SPM-ACI (4, 97%) whereas all other compounds showed activities comparable or lower than trolox. The most interesting compounds, namely ATRA-SPM-ATRA (3), 4, 10, 11 and 15, as well as unconjugated compounds such as ATRA and dopamine, were studied for their anti-inflammatory activity in vivo on rat paw oedema induced by Carrageenan and found to exhibit, for doses of 0.01 mmol/mL of conjugates per Kg of rat body weight, weaker anti-inflammatory activities (3.6-40%) than indomethacin (47%) with conjugate 3 being the most potent (40%) in this series of compounds. The cytocompatibility of selected compounds was evaluated by the viability of RAMEC cells in the presence of different concentrations (0.5-50 mu M) of the compounds. Conjugates 3 (IC50 2.6 mu M) and 4 (IC50 4.7 mu M) were more cytotoxic than the corresponding unconjugated retinoids ATRA (IC50 18.3 mu M) and ACI (IC50 14.6 mu M), whereas conjugate 15 (IC50 12.9 mu M) was less cytotoxic than either DCSP (IC50 11.3 mu M) or the tert-butyl ester of TRAA (IC50 2.9 mu M). (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of piplartine analogs and preliminary findings on structure–antimicrobial activity relationship
  作者：Antonio Maciel Fregnan、Guilherme Andrade Brancaglion、Alexandre Francisco Cerqueira Galvão、Cinara Oliveira D’Sousa Costa、Diogo Rodrigo Magalhães Moreira、Milena Botelho Pereira Soares、Daniel Pereira Bezerra、Naiara Chaves Silva、Stella Maria de Souza Morais、Josidel Conceição Oliver、Amanda Latercia Tranches Dias、Luiz Felipe Leomil Coelho、Diogo Teixeira Carvalho、Danielle Ferreira Dias、Thiago Belarmino de Souza

  DOI：10.1007/s00044-016-1774-9

  日期：2017.3

  In this work it is described the synthesis, characterization and antimicrobial and toxicity evaluation of a series of analogs of piplartine, a piperamide found in Piper sp. The compounds structures were confirmed by infrared spectroscopy, H-1, C-13 nuclear magnetic resonance, high resolution mass spectroscopy and were evaluated against strains of Candida spp., Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Derivative 24 was almost four-fold more potent (IC50: 48.83 mu M) and five-fold less toxic (SI > 3) than piplartine (IC50: 189.2 mu M; SI: 0.21) against Candida krusei, as well as two-fold more potent than fluconazole (IC50: 104.48 mu M). This compound was also active against Candida tropicalis at 97.67 mu M. Benzoyl derivative 17 was three-fold more potent (IC50: 85.2 mu M) and more than five-fold less toxic (CC50: 231.71 mu M) than piplartine (IC50: 315.33 mu M and CC50: 41.14 mu M) against Staphylococcus aureus. Given these findings, we have found analogs of piplartine which can be assumed as prototypes for the optimization and the development of new antimicrobial (compounds 24 and 17) agents.