Total Synthesis of Antitumor Antibiotic Derhodinosylurdamycin A

Abstract

The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by pinacol coupling to construct the tetracyclic angular aglycon, a Stille coupling of glycal stannane and tetracyclic aryliodide followed by stereoselective reduction to afford the 2-deoxy β-C-arylglycoside, and a late-stage stereoselective glycosylation for the preparation of derhodinosylurdamycin A. This synthetic strategy should be amenable to the chemical synthesis of analogs of derhodinosylurdamycin A bearing diverse 2-deoxy sugar subunits for structure and activity relationship studies.

Keywords: 2-deoxy sugars; antitumor antibiotic; derhodinosylurdamycin A; total synthesis; urdamycin.