Novel 9a,11-bridged azalides: One-pot synthesis of N′-substituted 2-imino-1,3-oxazolidines condensed to an azalide aglycone

An efficient one-pot method for the synthesis of novel 9a,11-bridged 15-membered 9a-aza-9-deoxo-9a-homoerythromycin A and its 6-O-methyl analogue has been developed. The novel bicyclic azalide scaffold is characterized by an N′-substituted-2-imino-1,3-oxazolidine moiety bound to a macrolactone ring between positions 9a and 11. Removal of the cladinose sugar from the starting compounds allows easy preparation of a small series of such bicyclic 3-keto and 3,6-hemiketal azalide derivatives. A mechanism for the formation of N′-substituted-2-imino-1,3-oxazolidines is discussed. Antibacterial properties of the prepared compounds were evaluated.