Hybrid Aminoglycoside Antibiotics via Tsuji Palladium-Catalyzed Allylic Deoxygenation

Biosynthetically inspired manipulation of the antibiotic paromomycin led, in six high-yielding steps, to a ring A harboring an α,β-unsaturated 6′-aldehyde and an allylic 3′-methylcarbonate group. Tsuji deoxygenation in the presence of 5 mol % Pd2(dba)3 and Bu3P granted access to a novel series of 3′,4′-dideoxy-4′,5′-dehydro ring A hybrids. The neomycin–sisomicin hybrid exhibited superior in vitro antibacterial activity to the parent compound neomycin.