Synthesis of Canthin-4-ones and Isocanthin-4-ones via B Ring Construction.

Abstract

Canthin-4-one is synthesized via a six-step procedure starting from commercially available 3-amino-4-bromopyridine in 26% overall yield. 3-Amino-4-bromopyridine is initially converted to 8-bromo-1,5-naphthyridin-4(1H)-one. O-Methylation, intermolecular Pd-catalyzed C-C coupling, and demethylation afford the key intermediate, 8-(2-chlorophenyl)-1,5-naphthyridin-4(1H)-one, for which intramolecular C-N coupling completes the synthesis of the canthin-4-one skeleton. Ten canthin-4-one analogues were prepared in addition to the parent compound. With minor modifications, the synthesis also applies to the synthesis of two series of isocanthin-4-ones.