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Scalable synthesis of highly stable cyclopropene building blocks: application for bioorthogonal ligation with tetrazines†
Lei Chen,Yuan Yang,Fei Li,Fei Jin,Bin He,Jun Yang
Organic Chemistry Frontiers Pub Date : 07/10/2023 00:00:00 , DOI:10.1039/D3QO00816A
Abstract

Cyclopropenes are small and highly reactive compounds; however, their synthesis poses significant challenges. This study presents a novel synthetic route for producing a stable and versatile cyclopropene precursor. This approach effectively addresses the issues related to instability, low boiling points, and difficulties in scale-up processes. Additionally, the cyclopropene precursor enabled the easy synthesis of various cyclopropenes with different functional groups and handles. Among the synthesized cyclopropene derivatives, the 1-methylcyclopropene uracil nucleoside derivative 40 had the highest second-order kinetic constant when reacting with the 5-TAMRA-Tz fluorescent dye. Specifically, the kinetic constant reached a value of 56.6 ± 1.94 M−1 s−1 when measured in pure phosphate-buffered saline solution.

Graphical abstract: Scalable synthesis of highly stable cyclopropene building blocks: application for bioorthogonal ligation with tetrazines
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