Stereoselective Synthesis and Biological Evaluation of C1-Epimeric and Desmethyl Monomeric Nuphar Analogues.

A class of monomeric nuphar analogues that are either epimeric at C1 and C1' or lack the naturally occurring methyl group at those positions were synthesized and evaluated for biological activity. The syntheses feature enantioselective vinylogous Mukaiyama-Mannich (vM-Mannich) reactions catalyzed by chiral phosphoric acids that proceed with excellent diastereoselectivity. Biological assays reveal that both the desmethyl and C1-epimeric monomeric nuphar analogous are able to induce rapid apoptosis.