An efficient, asymmetric solid-phase synthesis of benzothiadiazine-substituted tetramic acids: Potent inhibitors of the hepatitis C virus RNA-dependent RNA polymerase

An efficient, asymmetric solid-phase synthesis of benzothiadiazine-substituted tetramic acids is reported. Starting from commercially available chiral Fmoc-protected α-amino acids loaded onto Wang resin, Fmoc removal, reductive amination followed by amide bond formation, and base-catalyzed cyclization with simultaneous cleavage from the resin provided the desired products. Compounds described are potent inhibitors of the hepatitis C virus RNA-dependent RNA polymerase.

Solid-phase synthesis and SAR are described for a series of benzothiadiazine-substituted tetramic acid inhibitors of the hepatitis C virus RNA-dependent RNA polymerase, NS5B.Figure optionsDownload as PowerPoint slide