A novel series of acylide derivatives have been synthesized which exhibit in vitro potency against key respiratory pathogens. Modification of position 3 was accomplished by replacing different 3-O-substituted acyl groups in the macrolide core via a facile procedure. Compounds 7a-7i were eventually yielded by the conjunction of diverse hetero-aryl side chains with the 11-N,12-O-carbamate sub-structure.