Concise Synthesis of Functionalized Cyclobutene Analogues for Bioorthogonal Tetrazine Ligation

Abstract

Novel bioorthogonal tools enable the development of new biomedical applications. Here we report the concise synthesis of a series of aryl-functionalized cyclobutene analogues using commercially available starting materials. Our study demonstrates that cyclobutene acts as a small, strained dienophile to generate stable substrates suitable for bioorthogonal tetrazine ligation.

Keywords

• functionalized cyclobutene analogues
• concise synthesis
• tetrazine ligation
• bioorthogonal chemistry