Synthesis of benz[d]indeno[1,2-b]pyran-5,11-diones: versatile intermediates for the design and synthesis of topoisomerase I inhibitors

  • Bioorg Med Chem Lett. 2006 Apr 1;16(7):1846-9. doi: 10.1016/j.bmcl.2006.01.008.
Andrew Morrell  1 ,  Smitha Antony ,  Glenda Kohlhagen ,  Yves Pommier ,  Mark Cushman
Affiliations
  • 1. Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
PMID: 16442283 DOI: 10.1016/j.bmcl.2006.01.008
Abstract

A method has been developed that relies on a two-step, one-pot condensation between phthalide and 2-carboxybenzaldehydes to provide benz[d]indeno[1,2-b]pyran-5,11-diones in a multi-gram fashion. Treatment of these compounds with a primary amine allows rapid access to various N-substituted indenoisoquinolines, whose in vitro Anticancer activity and Topoisomerase I inhibition have been evaluated.