This proposal outlines a synthesis of the cytotoxic agent pluramycin, to aid in the development of compounds to treat human cancers. It is expected that this strategy will also provide access to the related antibiotics hedamycin and kidamycin. Additionally, this convergent approach should allow the incorporation of novel sugar residues and side chains to provide an array of potentially bioactive compounds. Pluramycin belongs to a novel family of bis-C-aryl glycosides, which have been shown to bind to DNA and to inhibit the binding of transcription factors to DNA. This synthetic plan entails; 1. Synthesis of furanyl-C-glycoside substrates for the Diels-Alder reaction. 2. Construction of the CDE rings of pluramycin via a novel strategy involving Diels-Alder reactions of the furan derivatives and halo- substituted quinones. 3. Elaboration of the B ring of pluramycin via a second regio and chemoselective Diels-Alder reaction. 4. Elaboration of the A ring of pluramycin in a fashion which will allow the stereochemical determination of the final product, and which will delay the incorporation of photo-sensitive functionality until the end of the synthesis.
