The new convenient synthesis of novel γ-alkylidenebutenolides from 6-aminopenicillanic acid

Butenolides have good biological activity and serve as the important unit of pharmaceutical intermediates, of which gamma-alkylidenebutenolides have gained wide attention over the last past decades particularly. A simple and practical method for the synthesis of butenolide 6 and its 5-substituted analogues 7a-t via vinylogous aldol reaction from 6-aminopenicillanic acid (6-APA) with the ratio of Z/E isomers between 1.1/1.0 and 1.0/0 under mild conditions in 6 steps was first reported. Besides, we also reported the methanolysis behaviors of azetidinone fused oxazoline derivatives. All the synthesized gamma-alkylidenebutenolides are new and are currently being evaluated for their biological activities.