Application of partially aromatic ortho-quionone-methides for the synthesis of novel naphthoxazines with improved antibacterial activity

Starting from naphthols and morpholine and using ethyl glyoxylate as the aldehyde component in the modified Mannich reaction, new aminonaphthol derivatives substituted with 2-and 1-naphthol were synthesised. The stabilization of precursor bifunctional compounds via partially aromatic ortho-quinone methide intermediate was tested with different cyclic imines in [4 + 2] cycloaddition. Based on H-1 NMR analysis, in the case of new alpha-amino acid esters the formation of a single product has been assumed. The NOE spectrum proved that the relative configuration of the newly formed stereogenic centres was trans. The compounds have also been tested in bacteria in order to reduce or reverse antibiotic resistance. Compounds 13 and 14 could inhibit the efflux pump system in susceptible and methicillin-resistant Staphylococcus aureus strains.

Automated summary

New aminonaphthol derivatives were synthesized using ethyl glyoxylate as the aldehyde component in the modified Mannich reaction, and their precursor bifunctional compounds were stabilized via partially aromatic ortho-quinone methide intermediate. These compounds show potential to reduce or reverse antibiotic resistance in bacteria.