Asymmetric synthesis and biological evaluation of 3-nitro-2H-chromenes as potential antibacterial agents

A one-pot organocatalytic domino Henry/Michael/dehydration sequence of various salicylaldehyde derivatives with nitromethane as a dual-nucleophile is disclosed. This straightforward strategy assembles the optically active (R)-2-alkyl 3-nitro-2H-chromenes with good to excellent enantioselectivities (up to 93% ee) and a broad substrate scope. Preliminary in vitro antibacterial evaluation revealed most of the chiral 3-nitro-2H-chromene derivatives exhibit antibacterial activities against four Gram-positive bacteria. Compound 3p with two bromine substituents on the core scaffold was shown to be the best antibacterial agent in the series against S. aureus, B. subtilis and Bacillus cereus with minimal bactericidal concentration (MBC) values of 4?μg/mL, and against Staphylococcus epidermidis with a MBC value of 8?μg/mL.