Annulation strategies for benzo[b]fluorene synthesis: efficient routes to the kinafluorenone and WS-5995 antibiotics.
Intramolecular palladium-mediated arylation approaches to benzo[b]fluorenes have been investigated. The methodology has been applied in a short synthesis of tri-O-methylkinafluorenone, providing an effective alternative to Friedel-Crafts-based approaches. During the course of this work, an acid-promoted quinolactonization of naphthoquinones was also developed, providing direct access to either ortho or para isomers as desired. Application of this methodology in syntheses of the antibiotics WS-5995A, WS-5995C, and functional analogues was demonstrated, and antitumoral activity of this class was determined.
Qabaja
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Bioorganic and Medicinal Chemistry Laboratories, Department of Chemistry, Northeastern University, 360 Huntington Avenue, Boston, Massachussetts 02115-5000, USA.
Jones
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D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003374:Coumarins / Q000138:chemical synthesis*; D004354:Drug Screening Assays, Antitumor; D004563:Electrochemistry; D005449:Fluorenes / Q000138:chemical synthesis* / Q000494:pharmacology; D010165:Palladium; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D003374:Coumarins; D005449:Fluorenes; C416882:WS-5995 C; C416883:kinafluorenone; D010165:Palladium; C027838:WS-5995 A