GENERAL SYNTHETIC APPROACH TOWARDS THE ANGUCYCLINES

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An enantioselective and stereoselective synthesis of the angucycline antibiotics of the "aquayamycin-type" is proposed, including synthesis of the aglycone aquayamycin. Preparation of a key tetracyclic intermediate allows for a flexible approach to all members of this family through selective C- and O-glycosylation reactions. A mild acid catalyzed cyclization constructs the tetracyclic benz[a]anthracene core in enantiomerically pure form following a Schultz-type Birch reduction/alkylation sequence. Most of the angucylines show a wide array of biological activity, including antitumor, antibacterial and antiviral activity, as well as being enzyme inhibitors and inhibitors of blood platelet aggregation. Although nearly thirty antibiotics in this family share the same aglycone aquayamycin, to date, no synthesis has been reported.