Asymmetric synthesis and biological evaluation of 3-nitro-2H-chromenes as potential antibacterial agents. Issue 39 (26th September 2018)

• Record Type: Journal Article
• Authors: Li, Muyao; Zhao, Xiaofei; Yang, Wen; Zhong, Fangrui; Yuan, Lujiang; Ren, Qiao
• Is Part Of: Tetrahedron letters. Volume 59:Issue 39(2018)
• Page Start: 3511
• Page End: 3515
• Publication Date: 2018-09-26
• Subjects: Enantioselective organocatalytic synthesis -- Domino reaction -- 3-Nitro-2H-chromenes -- Antibacterial activity -- Takemoto's thiourea catalyst; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2018.07.046
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Various ( R )-2-alkyl-3-nitro-2 H -chromenes are synthesized via a Henry/Michael/dehydration domino reaction. High to excellent enantioselectivities are achieved. Most of R enantiomers exhibit moderate to excellent inhibition activities. The absolute configuration and substitution pattern have significant influence on the antimicrobial activity. ( R )-ethyl-2-(6, 8-dibromo-3-nitro-2 H -chromene) acetate is the best potential antibacterial agent. 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.