Synthesis and antibacterial evaluation of novel pleuromutilin derivatives

A series of novel pleuromutilin derivatives possessing thioether moiety has been synthesized via acylation reaction under mild conditions. Their in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by agar dilution method and Oxford cup assay. Among the 17 compounds screened, 14-O-[(4-methoxybenzamide-2- methylpropane-2-yl) thioacetate] mutilin 4i, 14-O-[(2-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin 5a and 14-O-[(4-aminobenzamide-2-methylpropane-2-yl) thioacetate] mutilin 5c were resulted as most active antibacterial agents.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of novel pleuromutilin derivatives were synthesized under very mild conditions. ► Synthesized compounds were evaluated for their antibacterial activity by agar dilution method and Oxford cup assay. ► Most of these compounds possess antibacterial activity. ► Three compounds 4i, 5a, 5c showed excellent antibacterial activity.