Modular Approach for Photoinduced Cycloaddition Enabling the Synthesis of Diverse Bioactive Oxazoles

The synthesis of bioactive oxazoles is often inefficient, and the reported methods remain largely unexplored for complex derivatives. To circumvent this issue, we have utilized a metal-free, photomediated [3 + 2] cycloaddition reaction between diazo compounds and nitriles, leading to a step- and reagent-economical synthesis of bioactive oxazoles. These exciting developments guided us in the efficient synthesis of oxazole-based natural products like annuloline, alkaloids like pimprinethine, labradorin 2, and oxazole-containing pharmaceuticals such as oxaprozin. Utilizing this approach, we have also demonstrated efficient synthesis of deuterium-labeled and heterocyclic-based oxazoles.生物活性恶唑（oxazoles）的合成通常效率低下，且已报道的合成方法针对复杂衍生物的应用仍未得到充分挖掘。为解决这一难题，我们采用了无金属、光介导的重氮化合物（diazo compounds）与腈类（nitriles）之间的[3+2]环加成反应，实现了兼具步骤经济性与试剂经济性的生物活性恶唑合成路线。得益于这一研究进展，我们高效合成了含恶唑环的天然产物（如安诺林（annuloline））、生物碱类化合物（如品普林汀（pimprinethine）、拉布拉多林2（labradorin 2）），以及含恶唑环的药物如奥沙普秦（oxaprozin）。利用该合成策略，我们还实现了氘代标记以及杂环取代恶唑类化合物的高效制备。