Joining MCRs, Drug Discovery and Organocatalysis: Synthesis of Novel 3,3-Spirooxindoles Fused with Thiazolidines as New Potentially Bioactive Molecules

2-Oxindoles, especially 3,3-disubstituted or spiro-fused derivatives, are recognized as highly relevant compounds for drug discovery. In particular, a great interest appeared towards oxindole-based thiazolidine compounds1 as antitumor agents, for the inhibition of the p53-MDM2 protein-protein interaction. As part of our interest2 in multicomponent reactions (MCRs), we turned our attention to the almost unexplored Asinger reaction3 to form a thiazoline ring fused to the oxindole scaffold. Subsequently, this intermediate was subjected to a Joullié-Ugi 3-CR to give the target products in a highly efficient sequence. This combination of two sequential MCRs allowed us to synthesize a highly diverse library of spiro[indoline-3,2'-thiazolidin]-2-one derivatives. Finally, to enhance our work, we are developing an asymmetric organocatalytic approach for the synthesis of Asinger intermediates. References 1 Bertamino A.; Soprano M.; Musella S.; Rusciano M.R.; Sala M.; Vernieri E.; Di Sarno V.; Limatola A.; Carotenuto A.; Cosconati S.; Grieco P.; Novellino E.; Illario M.; Campiglia P.; Gomez-Monterrey I. J. Med. Chem., 2013, 56, 5407-5421. 2 Stucchi M.; Lesma G.; Meneghetti F.; Rainoldi G.; Sacchetti A.; Silvani A. J. Org. Chem., 2016, 81, 1877-1884. 3 Asinger F. Angew. Chem., 1956, 68, 377.