德国亚琛工业大学Leonori Daniele团队报道了噻唑、异噻唑和其他噻唑的光化学排列。相关研究成果发表在2024年11月13日出版的《自然》。

噻唑和异噻唑是药物和农用化学品发现中的重要基序。这些衍生物的合成通常是根据具体情况进行处理、设计和开发的。有时，缺乏针对给定靶标的稳健合成方法可能会造成重大困难，甚至阻碍特定衍生物的制备以供进一步研究。

该文中，研究人员报告了一种概念上不同的方法，即光化学照射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。在光激发下，这些衍生物填充了它们的π，π*单重态，这些单重态经历了一系列结构重排，导致环状体系及其取代基的整体置换。

这意味着，一旦制备了初始的杂芳族支架，它就可以通过选择性结构置换作为进入其他分子的入口点。这种方法在温和的光化学条件下运行，可以耐受复杂的支架和化学上不同的功能。

初步研究结果还表明，该方法有可能扩展到其他唑体系，包括苯并[d]异噻唑、吲唑、吡唑和异恶唑。该策略将光化学置换确立为一种强大而方便的方法，用于从更多可用的结构异构体制备复杂且难以获得的衍生物。

附：英文原文

Title: Photochemical permutation of thiazoles, isothiazoles and other azoles

Author: Roure, Baptiste, Alonso, Maialen, Lonardi, Giovanni, Yildiz, Dilara Berna, Buettner, Cornelia S., dos Santos, Thiago, Xu, Yan, Bossart, Martin, Derdau, Volker, Mndez, Mara, Llaveria, Josep, Ruffoni, Alessandro, Leonori, Daniele

Issue&Volume: 2024-11-13

Abstract: Thiazoles and isothiazoles are privileged motifs in drug and agrochemical discovery.1,2 The synthesis of these derivatives is generally approached, designed and developed on a case-by-case basis. Sometimes, the lack of robust synthetic methods to a given target can pose significant difficulties or even thwart the preparation of specific derivatives for further study.3,4 Here, we report a conceptually different approach whereby photochemical irradiation can be used to alter the structure of thiazoles and isothiazoles in a selective and predictable manner. Upon photoexcitation, these derivatives populate their π,π* singlet 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 which tolerate complex scaffolds and chemically distinct functionalities. Preliminary findings also indicate 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.

DOI: 10.1038/s41586-024-08342-8

Source: https://www.nature.com/articles/s41586-024-08342-8