Inverse Electron-Demand Diels-Alder Bioconjugation Reactions Using 7-Oxanorbornenes as Dienophiles

Oligonucleotides, peptides, and peptide nucleic acids incorporating 7-oxanorbornene as a dienophile were reacted with tetrazines linked to either a peptide, D-biotin, BODIPY, or N-acetyl-D-galactosamine. The inverse electron-demand Diels-Alder (IEDDA) cycloaddition, which was performed overnight at 37 degrees C, in all cases furnished the target conjugate in good yields. IEDDA reactions with 7-oxanorbornenes produce a lower number of stereoisomers than that of IEDDA cycloadditions with other dienophiles.