Simple Strategy for Benzo[de]chromene-7,8-dione Synthesis via Tandem Sonogashira Coupling and Intramolecular Cyclization Reactions

Benzo[de]chromene-7,8-dione derivatives are known to have important biological and pharmacological properties. Thus, a novel and efficient method was developed for the synthesis of benzo[de]chromene-7,8-dione derivatives via the tandem reaction of 5-bromo-2-hydroxynaphthalene-1,4-dione and terminal alkynes, which proceeds under the typical reaction conditions for Sonogashira coupling using Pd and Cu catalysts. The process likely occurs via a tandem reaction due to the synthesized Sonogashira coupling product undergoing intramolecular cyclization in the presence of a Cu catalyst. This method is superior to existing synthesis methods in that it can access benzo[de]chromene-7,8-dione compounds without the post-oxidation of benzo[de]chromenes. Furthermore, it enables the direct supply of several biologically active compounds. The minimum inhibitory concentrations (MICs) of the synthesized compounds against multidrug efflux pump-deficient strains of S. aureus, E. coli, and P. aeruginosa and their parent strains were determined. Certain synthesized compounds exhibited strong antimicrobial activity, indicating that they are substrates for multidrug efflux pumps.

Automated summary

A novel and efficient method for synthesizing benzo[de]chromene-7,8-dione derivatives without post-oxidation of benzo[de]chromenes was developed. The synthesized compounds exhibited strong antimicrobial activity, particularly against multidrug efflux pump-deficient strains.