Wang Zhihan, Flores Quinton, Guo Hongye, Trevizo Raquel, Zhang Xiaochan, Wang Shihan
Department of Physical Sciences, Eastern New Mexico University, Portales, NM 88130, USA.
School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, China.
CrystEngComm. 2020 Dec 7;22(45):7847-7857. doi: 10.1039/D0CE01403F. Epub 2020 Oct 26.
Natural products are precious feedstock in drug discovery and sustainable materials. This work using crystal engineering strategy, visible light, and solvent-free cycloaddition successfully constructed two caffeic acid derivatives, -(1,2,3,4)-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylate and -(1,2,3,4)-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylic acid. Because of the multiple stereocenters, it is challenging to prepare those compounds using traditional organic synthesis methods. The crystal engineering Hirshfeld surface analysis and 2D intermolecular interaction fingerprints were applied to synthetic route design. The light resources used in this work was visible LED or free, clean, and renewable sunlight. The evidence suggested that pure stereoisomer was obtained demonstrating the stereospecificity and efficiency of the topochemical cycloaddition reaction. The derivatives exhibited free radical scavenging and antioxidant biological activities, as well as the potential inhibitory activity of fatty acid binding proteins. One of the derivatives is the precursor of the natural product Shimobashiric acid C which paves the way for the total synthesis and further study of Shimobashiric acid C. In addition, the derivatives possess photodegradability at a specific wavelength, which is very attractive for "green" degradable polymeric materials.
天然产物是药物发现和可持续材料中的珍贵原料。这项工作采用晶体工程策略、可见光和无溶剂环加成反应，成功构建了两种咖啡酸衍生物，即-(1,2,3,4)-2,4-双(3,4-二羟基苯基)环丁烷-1,3-二羧酸酯和-(1,2,3,4)-2,4-双(3,4-二羟基苯基)环丁烷-1,3-二羧酸。由于存在多个立体中心，使用传统有机合成方法制备这些化合物具有挑战性。晶体工程的赫希菲尔德表面分析和二维分子间相互作用指纹图谱被应用于合成路线设计。这项工作中使用的光源是可见光发光二极管或免费、清洁且可再生的阳光。证据表明获得了纯立体异构体，证明了拓扑化学环加成反应的立体特异性和效率。这些衍生物表现出自由基清除和抗氧化生物活性，以及对脂肪酸结合蛋白的潜在抑制活性。其中一种衍生物是天然产物岛叶酸C的前体，为岛叶酸C的全合成和进一步研究铺平了道路。此外，这些衍生物在特定波长下具有光降解性，这对于“绿色”可降解聚合物材料非常有吸引力。
