Synthesis and Antibacterial Activities of Linezolid Analogues with C₅‐thioether/N,S‐acetal Amide

The modification on the C 5 ‐side chain in Linezolid analogues development is sporadic owing to the fact that trivial alternation on this position always leads to significant loss of antibacterial activity and in many cases to complete inactivity. The present work focused on constructing the potent yet relatively unexplored C 5 ‐side chain of Linezolid, therefore various C 5 ‐thioethers were synthesized and evaluated for their antibacterial activities. The most potent candidates, hydroxyl thioether ( R )‐ 5 a , ( R )‐ 10 a , and ( R )‐ 5 r which featuring a linear N,S ‐acetal amide motif at the C 5 side chain, shown strong antibacterial activities with no observable cytotoxicity.