Roure Baptiste, Alonso Maialen, Lonardi Giovanni, Yildiz Dilara Berna, Buettner Cornelia S, Dos Santos Thiago, Xu Yan, Bossart Martin, Derdau Volker, Méndez María, Llaveria Josep, Ruffoni Alessandro, Leonori Daniele
Department of Chemistry, University of Manchester, Manchester, UK.
Institute of Organic Chemistry, RWTH Aachen University, Aachen, Germany.
Nature. 2025 Jan;637(8047):860-867. doi: 10.1038/s41586-024-08342-8. Epub 2024 Nov 13.
Thiazoles and isothiazoles are privileged motifs in drug and agrochemical discovery. The synthesis of these derivatives is generally approached, designed and developed on a case-by-case basis. Sometimes, the lack of robust synthesis methods to a given target can pose considerable difficulties or even thwart the preparation of specific derivatives for further study. Here we report a conceptually different approach in which photochemical irradiation can be used to alter the structure of thiazoles and isothiazoles in a selective and predictable manner. On photoexcitation, these derivatives populate their π,π* singlet excited states that undergo a series of structural rearrangements, leading to an overall permutation of the cyclic system and its substituents. This means that once the initial heteroaromatic scaffold has been prepared, it can then function as an entry point to access other molecules by selective structural permutation. This approach operates under mild photochemical conditions that tolerate many chemically distinct functionalities. Preliminary findings also show the potential for extending this method to other azole systems, including benzo[d]isothiazole, indazole, pyrazole and isoxazole. This strategy establishes photochemical permutation as a powerful and convenient method for the preparation of complex and difficult-to-access derivatives from more available structural isomers.
噻唑和异噻唑是药物和农用化学品发现领域中备受关注的结构单元。这些衍生物的合成通常是根据具体情况进行设计和开发的。有时，缺乏针对特定目标的可靠合成方法可能会带来相当大的困难，甚至阻碍特定衍生物的制备以供进一步研究。在此，我们报告一种概念上不同的方法，即光化学辐照可用于以选择性和可预测的方式改变噻唑和异噻唑的结构。光激发时，这些衍生物会跃迁到π,π*单重激发态，经历一系列结构重排，导致环状体系及其取代基的整体排列变化。这意味着一旦制备出初始的杂芳基骨架，它就可以作为通过选择性结构排列获取其他分子的切入点。该方法在温和的光化学条件下进行，能耐受许多化学性质不同的官能团。初步研究结果还表明，将该方法扩展到其他唑类体系（包括苯并[d]异噻唑、吲唑、吡唑和异恶唑）具有潜力。这种策略确立了光化学排列作为一种从更易获得的结构异构体制备复杂且难以获得的衍生物的强大而便捷的方法。
