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How Enzyme Selectivity and Immobilization Affect Catalytic Yields in Lipase-Catalyzed Processes 酶的选择性和固定化如何影响脂肪酶催化过程的催化产量
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-09-10 DOI: 10.2174/0115701786330890240826053103
Ibrahim Karume
: Herein, the influence of structural attributes, including the interactions of lipases with support systems, substrates, products/byproducts, and the media environment, on enzyme stability, selectivity and activity are discussed. Substrates/products, such as methanol, glycerol, phenolic acids and polyphenols, can inhibit lipase activity by influencing the mass flow of the reactants and products or by enzyme denaturation, which is also caused by extreme pH, high temperatures, and digestive action of most organic solvents. Immobilization techniques that involve chemical bonding between the functional groups of the support and the amino acids of the lipase maintain the enzyme’s active conformation via the formation of stable secondary structures. Functionalized metal nanoparticles and metal and covalent organic frameworks (COFs and MOFs) covalently bond to lipases, reducing the reliance of the active site conformation on hydrogen bonding and disulfide bonds. The crystallinity of COFand MOF-immobilized lipases allows them to be used in contrasting media environments and at high temperatures, which increases the reaction kinetics and improves the catalytic yield. On the other hand, inert support systems such as silica promote catalytic yields by minimizing protein leaching, which fairly maintains the amount of the preloaded lipase. The structure of substrates also plays a large role, whereas some lipases strictly prefer narrow substrates. In contrast, others, such as Candida species lipases, are liberal and allow substrates of varying bulkiness/steric hindrances.
:本文讨论了结构属性对酶稳定性、选择性和活性的影响,包括脂肪酶与支持系统、底物、产物/副产物以及介质环境之间的相互作用。底物/产物(如甲醇、甘油、酚酸和多酚)可通过影响反应物和产物的质量流或酶变性来抑制脂肪酶的活性,极端 pH 值、高温和大多数有机溶剂的消化作用也会导致酶变性。固定化技术涉及支撑物的功能基团与脂肪酶氨基酸之间的化学键合,通过形成稳定的二级结构来保持酶的活性构象。功能化金属纳米颗粒以及金属和共价有机框架(COFs 和 MOFs)与脂肪酶共价结合,减少了活性位点构象对氢键和二硫键的依赖。COF 和 MOF 固定化脂肪酶的结晶性使它们可以在不同的介质环境和高温下使用,从而提高了反应动力学和催化产率。另一方面,惰性支持系统(如二氧化硅)可最大限度地减少蛋白质浸出,从而提高催化产率,这也相当程度地保持了预载脂肪酶的数量。底物的结构也起着很大的作用,有些脂肪酶严格偏好狭窄的底物。与此相反,其他脂肪酶(如念珠菌脂肪酶)则比较宽松,允许使用不同松厚度/星状阻碍的底物。
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引用次数: 0
Photochemical Dimerization of Indones: A DFT Study 印度尼西亚的光化学二聚化:DFT 研究
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-09-03 DOI: 10.2174/0115701786313908240822100732
Maurizio D' Auria
In this study, DFT calculations were performed in order to identify the reaction products of the photochemical dimerization of indones. Calculations allowed us to assume that all tested reactions occurred in the first excited singlet state. The irradiation of 2-phenyl-5-nitroindone gave the main product, the <i>anti-cis</i> head-to-tail dimer, while the other two compounds found in the experiments were the <i>syn-cis</i> head-to-head dimer and the <i>anti-cis</i> head-to-tail dimer. The irradiation of 2-phenylindone gave the main product, <i>syn-cis</i>-head-to-tail dimer, while the minor products were <i>anti-cis</i>-head-to-tail and <i>anti-cis</i>-head-to-head dimer. The photochemical dimerization of 2-methyl-3-phenylindone gave the main product, <i>anti-cis</i>-head-to-tail dimer, while the minor component of the mixture was <i>syn-cis</i>-head- to-head dimer.
在本研究中,我们进行了 DFT 计算,以确定吲哚酮光化学二聚化的反应产物。通过计算,我们假设所有测试反应都发生在第一激发单线态。辐照 2-苯基-5-硝基茚酮得到的主要产物是<i>反顺式</i>头尾二聚体,而实验中发现的另外两种化合物是<i>同顺式</i>头尾二聚体和<i>反顺式</i>头尾二聚体。辐照 2-苯基茚酮得到的主要产物是<i>同顺式</i>头尾二聚体,次要产物是<i>反顺式</i>头尾二聚体和<i>反顺式</i>头尾二聚体。2-甲基-3-苯基茚酮的光化学二聚反应得到的主要产物是<i>反顺式</i>-头尾二聚物,而混合物中的次要成分是<i>同顺式</i>-头尾二聚物。
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引用次数: 0
Rapid and Metal-Free Green Synthesis of Coumarins Catalyzed by Humic Acid 腐植酸催化香豆素的快速无金属绿色合成
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-09-03 DOI: 10.2174/0115701786318539240822112936
Ling Wei, Yichun Wang, Qixuan Huang, Hongshe Wang
: In recent years, numerous methods have been developed for the synthesis of coumarins via Pechmann reaction catalyzed by various catalysts. Although each of the synthetic strategies previously reported has its own merit, most of these methods are associated with certain disadvantages, including the use of commercially unavailable metal catalysts and organic solvents, low yields, and long reaction times. Therefore, the development of a highly efficient, green, and sustainable catalytic methodology for the synthesis of coumarins is still desirable. Humic acid has been found to be an efficient catalyst for the synthesis of coumarins via the Pechmann reaction at 80oC under solvent-free conditions. The methodology enables the synthesis of structurally diverse coumarins from phenols and β-keto esters within 5-8 min in high yields (91-99%). The green, commercially available, inexpensive organocatalyst can be effectively recycled and reused five times with no significant dropdown in the yield of the product. The method reported has the advantages of high yield, no need for metal catalysts, short reaction time, simple operation, and green and reusable catalyst.
:近年来,在各种催化剂的催化下通过佩赫曼反应合成香豆素的方法层出不穷。尽管之前报道的每种合成策略都有其优点,但这些方法大多存在一些缺点,包括使用市面上买不到的金属催化剂和有机溶剂、产量低、反应时间长等。因此,开发一种高效、绿色和可持续的催化方法来合成香豆素仍然是很有必要的。研究发现,腐植酸是一种高效催化剂,可在 80oC 无溶剂条件下通过 Pechmann 反应合成香豆素。该方法可在 5-8 分钟内从苯酚和 β-酮酯合成结构多样的香豆素类化合物,产率高(91-99%)。这种可从市场上买到的绿色廉价有机催化剂可以有效地回收和重复使用五次,而且产品收率没有明显下降。所报告的方法具有产率高、无需金属催化剂、反应时间短、操作简单、催化剂绿色环保且可重复使用等优点。
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引用次数: 0
An Efficient Metal-Free Methodology for the Synthesis of Hydrazo-Linked 5-(4-aryl)-1H-1,2,4-Triazoles 合成 5-(4-芳基)-1H-1,2,4-三唑的高效无金属方法学
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-08-28 DOI: 10.2174/0115701786332586240819074232
Neha Rani, Deepak K. Aneja, Mayank Kinger, Rinku Soni, Monika Sihag, Sandeep Malik, Kirti Bhardwaj
Hydrazo compounds have displayed significant roles in both biological and physical aspects, such as spinamycin as a potent growth inhibitor against fungi and rat sarcoma cells, hydrazo tocopherol as a component of vitamin E, and electron-rich hydrazo-linked triazines as energetic materials. In this study, a metal-free approach was proposed for the synthesis of hydrazo-linked 5-(4- aryl)-1H-1,2,4-triazoles. The methods for the synthesis of 5-(4-aryl)-1H-1,2,4-triazoles initiated by the reaction of aldehyde with semicarbazide. The resulted compound, 5-(4-aryl)-1H-1,2,4-triazol-3- ol, upon reaction with phosphorous oxychloride yielded 3-chloro-5-(4-aryl)-1H-1,2,4-triazoles. These synthesized compounds upon fusión with various aryl and hetero aryl substituted hydrazines provided desired hydrazo moieties. Synthesized hydrazo compounds were characterized by spectroscopic techniques, viz. 1H-NMR, FT-IR and mass spectrometry. In this study, a series of novel hydrazo- linked 5-(4-aryl)-1H-1,2,4-triazoles were synthesized. The methodology proposed in this study eliminates the use of complicated procedures and heavy metals.
偶氮化合物在生物和物理两方面都发挥了重要作用,如作为真菌和大鼠肉瘤细胞强效生长抑制剂的旋光霉素、作为维生素 E 成分的生育酚偶氮,以及作为高能材料的富电子偶氮连接三嗪。本研究提出了一种无金属的方法来合成肼联 5-(4-芳基)-1H-1,2,4-三唑。合成 5-(4-芳基)-1H-1,2,4-三唑的方法始于醛与缩氨基脲的反应。得到的 5-(4-芳基)-1H-1,2,4-三唑-3-醇化合物与氧氯化磷反应后生成 3-氯-5-(4-芳基)-1H-1,2,4-三唑。这些合成化合物在与各种芳基和杂芳基取代的肼反应后,得到了所需的偶氮分子。合成的偶氮化合物通过光谱技术(即 1H-NMR、FT-IR 和质谱)进行表征。在本研究中,合成了一系列新颖的联氮 5-(4-芳基)-1H-1,2,4-三唑。本研究提出的方法无需使用复杂的程序和重金属。
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引用次数: 0
Ce(OTf)3-Catalyzed Synthesis of Glucopyranurono-6,1-Lactone: A Key Intermediate for Obtaining Glycoconjugates of Peptidic Fragments of Arenastatin A Ce(OTf)3催化合成吡喃葡萄糖醛酸-6,1-内酯:获得阿瑞司他丁 A 肽片段糖苷共轭物的关键中间体
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-08-28 DOI: 10.2174/0115701786325021240817182955
A. Mezrai, L. Mrah, Z. Khiati, A. Keniche
In this work, 2,3,4-tri-O-acetyl-D-glucurono-6,1-lactone has been prepared from glucuronic acid in two steps by converting it into glucuronic anhydride. In the presence of a catalytic amount of Ce(OTf)3 (10 examples) in ethyl acetate, the glucuronic anhydride provided 6.1-lactone in good to excellent yields. This lactone was used to prepare the novel glycoconjugates of peptidic fragments of arenastatin A, a sponge cytotoxic depsipeptide, and its analogues.
在这项工作中,通过将葡萄糖醛酸转化为葡萄糖醛酸酐,分两步从葡萄糖醛酸制备出了 2,3,4-三-O-乙酰基-D-葡萄糖醛酸-6,1-内酯。在乙酸乙酯中存在催化量的 Ce(OTf)3(10 例)的情况下,葡萄糖醛酸酐以良好至极好的收率提供了 6.1-内酯。这种内酯被用来制备新型的阿那斯丁 A(一种海绵细胞毒性去肽类化合物)肽片段糖共轭物及其类似物。
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引用次数: 0
Continuous Flow Synthesis of Amides in Bio-Derived Solvent GVL 在生物衍生溶剂 GVL 中连续流合成酰胺
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-08-23 DOI: 10.2174/0115701786313379240815113722
Xu-Yang Mu, Rui Zhu, Li-Jie Yu, Wen-Long Wang
: The amide group is one of the most ubiquitous chemical motifs in the pharmaceutical field. An efficient continuous flow synthesis of amides was achieved by coupling acids with amines using 2-bromo-1-ethylpyridinium tetrafluoroborate (BEP) in the bio-derived “green” solvent γ- valerolactone (GVL). The reaction proceeded under mild reaction conditions (ambient temperature, 1 min) with simple filtration without the need for extensive purification, allowing a safe and ondemand generation of procainamide and VH032-Boc with a productivity of 0.44 g day-1 and 0.99 g day-1. The finding of our work aligned with green chemistry principles should result in its adoption by the chemistry community. other: No
:酰胺基团是制药领域最常见的化学结构之一。通过使用 2-溴-1-乙基吡啶鎓四氟硼酸盐(BEP)在生物衍生的 "绿色 "溶剂γ-戊内酯(GVL)中将酸与胺偶联,实现了酰胺的高效连续流合成。反应在温和的反应条件下进行(环境温度,1 分钟),只需简单过滤,无需大量纯化,即可安全地按需生成普鲁卡因酰胺和 VH032-Boc,生产率分别为 0.44 克/天和 0.99 克/天。我们的研究结果符合绿色化学原则,因此应被化学界采用:无
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引用次数: 0
One-Pot Syntheses and Enzyme Inhibition Studies of New C-28 Ester Derivatives of Betulinic Acid 白桦脂酸 C-28 酯新衍生物的一锅合成和酶抑制研究
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-08-12 DOI: 10.2174/0115701786324362240726102810
Muhammad Shaiq Ali, Sumera Shezadi, Azra Akbar, Humaira Zafar, Muhammad Imran Malik, Mahreen Lateef
: Betulinic acid and its various synthetic derivatives have been reported to possess diverse biological activities and some of these may serve as useful therapeutic agents for a variety of human disorders. In this perspective, we have now developed convenient one-pot syntheses of new C-28 esters (2-7) of betulinic acid by esterification of the carboxylic moiety of betulinic acid (1) with various alkylating agents. All the target compounds were subjected to enzyme inhibition studies to ascertain their possible therapeutic utility. Compound 5 showed very potent lipoxygenase inhibitory activity with an IC50 value of 13.2 μM, being much lower than the IC50 value of 22.4 μM of baicalein, which was used as the standard. Butulinic acid itself and compound 6 also showed significant inhibitory potential (IC50: 32.4 and 25.1 μM) against the same enzyme. The activities of both compounds 5 and 6 have been justified by intensive docking studies. Compounds 2 and 3 exhibited substantial inhibition (IC50: 18.4 and 21.5 μM) against the enzyme butrylcholinesterase, compared to serine used as the standard (IC50: 7.8 μM).
:据报道,白桦脂酸及其各种合成衍生物具有多种生物活性,其中一些可作为治疗各种人类疾病的有用药物。从这个角度出发,我们通过白桦脂酸(1)的羧基与各种烷化剂的酯化反应,开发出了方便的白桦脂酸 C-28 新酯(2-7)的一锅合成方法。对所有目标化合物都进行了酶抑制研究,以确定其可能的治疗作用。化合物 5 显示出非常强的脂氧合酶抑制活性,其 IC50 值为 13.2 μM,远低于作为标准的黄芩素的 IC50 值 22.4 μM。丁二酸本身和化合物 6 也对同一种酶表现出明显的抑制潜力(IC50:32.4 和 25.1 μM)。深入的对接研究证明了化合物 5 和 6 的活性。与作为标准物质的丝氨酸(IC50:7.8 μM)相比,化合物 2 和 3 对丁酰胆硷酯酶具有很强的抑制作用(IC50:18.4 和 21.5 μM)。
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引用次数: 0
Molecular Docking and Modelling Studies for Identifying Novel Oxadiazole Derivatives to Inhibit COX-2 Enzyme as an Anti-Inflammatory Treatment 识别新型噁二唑衍生物的分子对接和建模研究,以抑制 COX-2 酶作为一种抗炎疗法
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-08-12 DOI: 10.2174/0115701786314768240726053647
Tarun Chaudhary, Prabhat Kumar Upadhyay, Ritu Kataria
The objective of the study was to develop new Oxadiazole compounds using docking simulation studies for inhibitory action against the Cycloxoygenase-2(COX-2) enzyme. The study aimed at the development and identification of novel and potent derivatives of 1,3,4-oxadiazole for targeting anti-inflammatory disease by screening their inhibitory action against COX-2 enzyme with schrodinger molecular docking software and molecular simulation by GROMACS 2022. A library of 375 novel compounds of 1,3,4-oxadiazoles derivatives was designed and proposed for docking against cyclooxygenase-2 enzyme (COX-2)PDB ID: 6BL4, which was downloaded from protein data bank site https://www.rcsb.org/. MD simulations for three models were performed, namely, compound A-Cox-2, E-Cox-2, and G-Cox-2, for 100 ns. Out of 375 proposed compounds, the top 16 compounds with good docking scores and binding energy were selected for further ADME profile studies in which all compounds showed good results as compared to Standard drugs. RMSD values of 0.2 nm showed that all ligand-Cox-2 complexes were stable during simulation. Compound G was the most efficient in decent interactions with the residues ARG120 and TYR355 of cyclooxygenase- 2, which were stable for 29.32, 21.52, and 12.00% duration of simulation along with comparatively better h-bond contacts. All potential inhibitors met Lipinski's rule of five, indicating oral availability. The potential compounds may be further evaluated for pharmacological activities using different in vitro and in vivo evaluations.
这项研究的目的是利用对接模拟研究开发新的噁二唑化合物,以抑制环氧化酶-2(COX-2)酶的作用。该研究旨在通过施罗丁格分子对接软件和 GROMACS 2022 进行分子模拟,筛选 1,3,4-噁二唑对 COX-2 酶的抑制作用,从而开发和鉴定新型、强效的 1,3,4-噁二唑衍生物,用于抗炎。研究人员设计了一个由 375 个 1,3,4-噁二唑衍生物组成的新型化合物库,并建议将其与环氧化酶-2(COX-2)进行对接,PDB ID:6BL4,该数据库下载自蛋白质数据库网站 https://www.rcsb.org/。对三个模型,即化合物 A-Cox-2、E-Cox-2 和 G-Cox-2,进行了 100 ns 的 MD 模拟。在提出的 375 个化合物中,选取了对接得分和结合能较高的前 16 个化合物进行进一步的 ADME 图谱研究,与标准药物相比,所有化合物都显示出良好的结果。RMSD 值为 0.2 nm,表明所有配体-Cox-2 复合物在模拟过程中都很稳定。化合物 G 与环氧合酶 2 的残基 ARG120 和 TYR355 的相互作用最为有效,在模拟过程中分别稳定了 29.32%、21.52% 和 12.00%,同时具有相对较好的 h 键接触。所有潜在的抑制剂都符合利宾斯基的 5 项规则,表明可以口服。这些潜在化合物的药理活性可通过不同的体外和体内评价进行进一步评估。
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引用次数: 0
Insight into the Various Synthetic Approaches of 1,3,4 and 1,2,4-Oxadiazole and its Derivatives, Along with their Remarkable Biological Activities 深入了解 1,3,4 和 1,2,4- 恶二唑及其衍生物的各种合成方法及其显著的生物活性
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-08-08 DOI: 10.2174/0115701786318560240723060417
Sadhana Sharma, Chandana Majee, Rupa Mazumder, Kavita Rana, Swrupanjali Padhi, Avijit Mazumder, Saumya Das, Pankaj Kumar Tyagi, Sachin Kumar Singh
: Oxadiazole is an organic compound featuring a heterocyclic ring housing carbon, oxygen, and nitrogen atoms. Due to their heightened stability in biological environments, oxadiazole rings exhibit significant biological activities, effectively addressing health challenges like infectious diseases and chronic conditions in medicinal chemistry. The main objective of this review is to discuss various synthetic approaches related to oxadiazole and its derivatives, along with their biological activities. The diverse reactivity positions oxadiazole as a valuable building block in organic synthesis, with derivatives exhibiting promising pharmacological activities. It involves a systematic literature review, critical analysis, and synthesis of existing research. This review comprises the everexpanding chemical knowledge but also holds significant implications for drug development. The various synthetic approaches, such as Suzuki-Miyaura, Stille coupling [3+2] cycloaddition reaction, and many more methods used for the synthesis of oxadiazole through different schemes, have been discussed thoroughly. This review also concisely associated the pharmacological activities of new oxadiazole and its derivatives, such as prenoxdiazine, dapagliflozin, nesapidil, pleconaril, and so on. This review highlights the importance of continued research into the structure-activity relationships of oxadiazole derivatives, paving the way for developing novel and more potent therapeutic agents.
:噁二唑是一种有机化合物,具有一个包含碳、氧和氮原子的杂环。由于其在生物环境中的高度稳定性,恶二唑环具有显著的生物活性,可有效解决药物化学中的传染性疾病和慢性疾病等健康难题。本综述的主要目的是讨论与噁二唑及其衍生物有关的各种合成方法及其生物活性。噁二唑具有多种反应活性,是有机合成的重要构件,其衍生物具有良好的药理活性。这涉及到对现有研究的系统性文献回顾、批判性分析和综合。这篇综述不仅包含了不断扩展的化学知识,而且对药物开发具有重要意义。本综述深入讨论了各种合成方法,如 Suzuki-Miyaura、Stille 偶联 [3+2] 环加成反应,以及更多通过不同方案合成噁二唑的方法。本综述还简明扼要地介绍了新型噁二唑及其衍生物的药理活性,如普诺地嗪、达帕利嗪、奈沙地尔、哌氯地尔等。这篇综述强调了继续研究噁二唑衍生物结构-活性关系的重要性,为开发新型和更有效的治疗药物铺平了道路。
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引用次数: 0
Efficient Green Synthesis and Characterization of Benzil and its Derivatives Using Microwave Irradiation 利用微波辐照对苯齐及其衍生物进行高效绿色合成和表征
IF 0.8 4区 化学 Q4 CHEMISTRY, ORGANIC Pub Date : 2024-08-07 DOI: 10.2174/0115701786308700240801062008
Krina Patel, Drashti Shah, Dev Jani, Neel Savaliya, Dharti Patel, Ashish Shah, Pinkal Patel, Ashish Patel
: The main aim of the present work was to conduct the one-pot microwave-assisted green synthesis of benzil and its derivatives. Benzil is acknowledged as a pivotal scaffold in the realm of medicinal and organic chemistry, owing to its extensive utilities. Due to the various merits of the green technology approach compared to classical methodology and the provision of sustainable chemistry, this reaction has received renewed interest for preparing benzil derivatives in an environmentally friendly manner with improved yields. We have, herein, presented a highly efficient route for the synthesis of benzil derivatives utilizing acetophenone and benzene derivatives as primary substrates. Notably, this synthesis obviates the necessity for any potentially hazardous catalyst and employs microwave irradiation and iodine green oxidant to facilitate the reaction. All synthesized compounds were characterized by spectroscopic techniques, such as IR, 1H NMR, and mass spectrometry. A green and efficient microwave-assisted synthesis methodology for benzil and its derivatives has been developed using iodine green oxidant. This approach has yielded the desired benzil derivatives with remarkable efficiency, achieving yields ranging from 91% to 97% within a short time of 10-15 minutes; the derivatives have been characterized using spectral techniques, viz., IR, 1H NMR, and mass spectrometry. It is noteworthy that the entire reaction optimization process has been conducted in an environmentally friendly manner, thereby exemplifying a synthetic methodology being both environmentally sustainable and economically viable, compared to conventional techniques.
:本研究的主要目的是进行苯偶酰及其衍生物的单锅微波辅助绿色合成。苯偶酰因其广泛的用途而被公认为是药物和有机化学领域的关键支架。由于绿色技术方法与传统方法相比具有各种优点,而且提供了可持续化学,因此这种反应在以环境友好的方式制备苯偶酰衍生物并提高产率方面再次受到关注。在此,我们提出了一条利用苯乙酮和苯衍生物作为主要底物合成苯偶姻衍生物的高效路线。值得注意的是,这种合成方法无需使用任何潜在危险的催化剂,并采用微波辐照和碘绿氧化剂来促进反应。所有合成化合物都通过红外光谱、1H NMR 和质谱等光谱技术进行了表征。利用碘绿氧化剂开发了一种绿色高效的微波辅助合成苯偶姻及其衍生物的方法。这种方法能在 10-15 分钟的短时间内高效地合成出所需的苯偶酰衍生物,产率从 91% 到 97%不等;衍生物的特征已通过光谱技术(即红外光谱、1H NMR 和质谱分析)确定。值得注意的是,整个反应优化过程都是以对环境友好的方式进行的,因此与传统技术相比,这种合成方法既具有环境可持续性,又具有经济可行性。
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引用次数: 0
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Letters in Organic Chemistry
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