Total syntheses of riccardins A, B, and C, cytotoxic macrocyclic bis(bibenzyls) from liverworts

Abstract

Di-O-methylriccardin A (3), riccardin A (1), and riccardin B (4) were synthesized by convergent schemes. Rings A and D of both riccardin A and B, as well as rings B and C of riccardin B were joined by the Ullmann ether synthesis. The aryl-aryl bond in riccardin A was established by Ni(0)-assisted intramolecular coupling of a di-iodoester (17). Rings A and B were linked in all syntheses by the Wittig reaction, whereas ring closure was effected by a tetraphenylethene catalyzed Wurtz reaction. Demethylation of (3) gave riccardin C (2).