Design and synthesis of an all-in-one 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group for photo-affinity labeling.
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.
Kumar
Nag S
NS
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Young
Robert N
RN
D001386:Azides / Q000737:chemistry; D001389:Azirines / Q000138:chemical synthesis* / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000737:chemistry; D010777:Photochemistry
C543933:3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl; D001386:Azides; D001389:Azirines; D006845:Hydrocarbons, Fluorinated; D019920:Photoaffinity Labels; D001710:Biotin; D000432:Methanol