Design and synthesis of an all-in-one 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group for photo-affinity labeling

作者：Kumar Nag S; Young Robert N^*

来源：Bioorganic & Medicinal Chemistry, 2009, 17(15): 5388-5395.

DOI：10.1016/j.bmc.2009.06.048

• Photo-affinity labeling
• Click chemistry
• 3-(1,1-Difluoroprop-2-ynyl)-3H-diazirin-3-yl group
• Leukotriene
• 5-Lipoxygenase

A novel radioisotope-free photo-affinity probe containing the 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group was designed and synthesized. This very compact functionality is envisaged to allow photochemically-induced coupling of a compound to its target followed by click reaction coupling with an azido-biotin reagent in order to facilitate purification of the labeled target. In a proof-of-concept study we have shown that 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group could be photolyzed to efficiently furnish the methanol adduct 23 and that the generated highly unstable carbene does not react with the neighboring acetylene moiety. A subsequent click reaction with the azido- biotin derivative 25 proceeded smoothly to give triazole 26. This chemical probe should thus be of unique value for facilitating identification of the molecular structure of the target of a bioactive compound.

• 出版日期2009-8-1