Uguen Mélanie, Gai Conghao, Sprenger Lukas J, Liu Hang, Leach Andrew G, Waring Michael J
Cancer Research UK Drug Discovery Unit, Newcastle University Centre for Cancer, Chemistry, School of Natural and Environmental Sciences, Newcastle University Bedson Building Newcastle upon Tyne NE1 7RU UK
Organic Chemistry Group, College of Pharmacy, Naval Medical University Shanghai 200433 P. R. China.
RSC Adv. 2021 Oct 5;11(48):30229-30236. doi: 10.1039/d1ra05539a. eCollection 2021 Sep 6.
4-Oxobutenoic acids are useful as biologically active species and as versatile intermediates for further derivatisation. Currently, routes to their synthesis can be problematic and lack generality. Reaction conditions for the synthesis of 4-oxo-2-butenoic acid by microwave-assisted aldol-condensation between methyl ketone derivatives and glyoxylic acid have been developed. They provide the desired products in moderate to excellent yields for a wide range of substrates, by applying a simple procedure to accessible starting materials. The investigation revealed different conditions are required depending on the nature of the methylketone substituent, with aryl derivatives proceeding best using tosic acid and aliphatic substrates reacting best with pyrrolidine and acetic acid. This substituent effect is rationalised by frontier orbital calculations. Overall, this work provides methods for synthesis of 4-oxo-butenoic acids across a broad range of substrates.
4-氧代丁酸作为生物活性物质以及用于进一步衍生化的通用中间体很有用。目前，其合成路线可能存在问题且缺乏通用性。已经开发出通过微波辅助甲基酮衍生物与乙醛酸之间的羟醛缩合反应合成4-氧代-2-丁烯酸的反应条件。通过对易得的起始原料采用简单的方法，它们能以中等至优异的产率为多种底物提供所需产物。研究表明，根据甲基酮取代基的性质需要不同的条件，芳基衍生物使用对甲苯磺酸反应效果最佳，脂肪族底物与吡咯烷和乙酸反应效果最佳。这种取代基效应通过前沿轨道计算得到了合理的解释。总体而言，这项工作提供了在广泛底物范围内合成4-氧代丁酸的方法。
