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 mug/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 mug/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
