4-Isocyanoindole-2ʹ-deoxyribonucleoside (4ICIN): An isomorphic indole nucleoside suitable for inverse electron demand Diels-Alder reactions

Isomorphic nucleosides are powerful tool compounds for interrogating a variety of biological processes involving nucleosides and nucleic acids. We previously reported a fluorescent isomorphic indole nucleoside called 4CIN. A distinguishing molecular feature of 4CIN is the presence of a 4-cyano moiety on the indole that functions as the nucleobase. Given the known chemical reactivity of isonitriles with tetrazines through [4+1]-cycloaddition chemistry, we investigated whether conversion of 4CIN to the corresponding isonitrile would confer a useful chemical probe. Here we report the synthesis of 4-isocyanoindole-2ʹ-deoxyribonucleoside (4ICIN) and the propensity of 4ICIN to undergo inverse electron demand Diels-Alder cycloaddition with a model tetrazine.