Regio‐ and Chemoselective 6′‐N‐Derivatization of Aminoglycosides: Bisubstrate Inhibitors as Probes To Study Aminoglycoside 6′‐N‐Acetyltransferases

Complex nanomolar inhibitors in one pot: Aminoglycoside–coenzyme A derivatives were prepared through an efficient regioselective 6′-N modification of aminoglycosides (see scheme). These bisubstrates show tight-binding competitive inhibition of aminoglycoside 6′-N-acetyltransferase, an enzyme involved in antibiotic resistance.