Synthesis and antimicrobial properties of 2H-pyran-3(6H)-one derivatives and related compounds.

The synthesis of several derivatives of 2H-pyran-3(6H)-ones and their Michael adducts is described. Phenylthio, benzenesulfonyl, p-acetylaminobenzenesulfonyl, and p-bromophenyl substituents are beneficial for activity against gram-positive bacteria. 2-[4-(Phenylthio)phenyl]-2-methyl-6-methoxy-2H-pyran-3(6H)-one (8a) showed a minimum inhibitory concentration of 1.56 micrograms/mL against Staphylococcus aureus ATCC 2593, and 2-[4-(phenylthio)phenyl]-2-methyl-6-[(p-nitrobenzoyl)oxy]-2H-pyran-3 (6H)-one (9) showed a minimum inhibitory concentration of 0.75 microgram/mL against Streptococcus sp. C203M. In general, derivatives of 6-hydroxy-2H-pyran-3(6H)-ones with substituents at C-2 and C-6 showed significant activity against gram-positive bacteria. More specifically, the bulkier the C-2 substituent, the greater the antibacterial activity. Michael adducts of thiols (13) showed activity, which may be due to a retro-Michael reaction. In conclusion, the alpha,beta-enone system is essential for the activity of 6-hydroxy-2H-pyran-3(6H)-ones, and the size and nature of substituents at C-2 are associated with antimicrobial activity.