3. An Asymmetric Organocatalytic Approach to Michael Reactions of Thiazolones and Nitroalkenes: Preparation of Compounds with Anti-Cancer Potency

Abstract:

Graphic Abstract: The utility of thiazole heterocycles in medicinal chemistry has attracted much attention in the construction of their derivatives. With the aid of a chiral organocatalyst developed from a cinchona alkaloid, a series of chiral thiazolone derivatives were prepared with excellent diastereo- and enantioselectivities. They were found to display strong inhibition of five types of cancer cells in vitro.

We present a highly efficient strategy for obtaining a series of chiral 2,4-disubstituted thiazolone derivatives with excellent diastereo- and enantioselectivities through the creation of carbon- and nitrogen-substituted quaternary carbon stereocenters. With the chiral tertiary amine-thiourea catalyst developed by our group, the reactions could be performed smoothly at 1 mol-% catalyst loadings without any additive. Preliminary biological evaluation demonstrated that these analogues could inhibit cell proliferation in vitro significantly.

Liu, X.; Chen, Q.; Li, W.; Liang, Y.; Wang, R* (2012) Synthesis of 3-Aroyl-4-hydroxy-4-arylpiperidine Derivatives by DBU-Catalyzed Reactions of Amines with Vinyl Ketones. Synlett, 1691-1695, DOI: 10.1055/s-0031-1291162.