CHEMICAL STRUCTURES AND SYNTHESIS OF THE DIYNENE CLASS ANTIBIOTICS

Recently, a series of novel antitumor antibiotics possessing an unprecedented bicyclodiynene unit have been discovered. Esperamicins, calicheamicins and dynemicins contain a bicyclo [7.3.1]-1,5-diyne-3-ene core substituted with an oligosaccharide or an anthraquinone. Neocarzinostatin chromophore is different from them having a bicyclo[7.3.0]-diyne chromophore. They display exceptionally potent cytotoxicity and antitumor activity. Their strong activity has been ascribed to DNA damage resulting from hydrogen abstraction from the sugar backbone by the diradical species generated by Bergman cyclization of the diynene upon triggering. Their oligosaccharide or aromatic side chain plays as DNA recognition site allowing the diynene to be positioned for cutting reaction in DNA. The discoveries of these antibiotics have launched numerous synthetic ventures directed to total syntheses and simple model syntheses. Many diynene aglycones and pseudosaccharides have already been synthesized and some synthetic cyclic and acyclic diynene models showed DNA cutting and cytotoxic activity. The results strongly suggest potentiality of those and related molecules to be novel anticancer agents.