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

Abstract 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-2 H -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-2 H -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.