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There is an urgent need to discover new antibiotics and improve the efficacy of known antibiotics against Gram-negative bacteria. “Trojan horse” conjugates are novel and promising antibiotics. Herein we report the design and synthesis of vitamin-B12–ampicillin conjugates, which exhibited more than 500 times improved activity against Escherichia colicompared with ampicillin itself. Our studies demonstrate that the vitamin-B12uptake pathway could be employed for effective antibiotic delivery and efficacy enhancement.

An efficient method for the synthesis of azabicyclo[5.1.0]octenes through cycloisomerization of nitrogen-tethered 1,7-enynes catalyzed by [IrCp*Cl2]2was developed. With appropriately designed substrates, this method could be easily employed to generate complex fused ring systems such as [6-6-3-7], [5-6-3-7], [7-6-3-7], and [8-6-3-7] ring systems, which enriches the diversity of the cyclopropane-fused polycycle library, and has potential applications in SAR studies of pharmaceutically interesting compounds and total synthesis of natural products.