Synthesis of (±)-Idarubicinone via Global Functionalization of Tetracene

David G. Dennis, Mikiko Okumura, David Sarlah

Research output: Contribution to journalArticle

Abstract

Anthracyclines are archetypal representatives of the tetracyclic type II polyketide natural products that are widely used in cancer chemotherapy. Although the synthesis of this class of compounds has been a subject of several investigations, all known approaches are based on annulations, relying on the union of properly prefunctionalized building blocks. Herein, we describe a conceptually different approach using a polynuclear arene as a starting template, ideally requiring only functional decorations to reach the desired target molecule. Specifically, tetracene was converted to (±)-idarubicinone, the aglycone of the FDA approved anthracycline idarubicin, through the judicious orchestration of Co- and Ru-catalyzed arene oxidation and arenophile-mediated dearomative hydroboration. Such a global functionalization strategy, the combination of site-selective arene and dearomative functionalization, provided the key anthracycline framework in five operations and enabled rapid and controlled access to (±)-idarubicinone.

Original languageEnglish (US)
Pages (from-to)10193-10198
Number of pages6
JournalJournal of the American Chemical Society
Volume141
Issue number26
DOIs
StatePublished - Jul 3 2019

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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