Development of a convergent entry to the diazofluorene antitumor antibiotics: enantioselective synthesis of kinamycin F

J Am Chem Soc. 2010 Mar 3;132(8):2540-1. doi: 10.1021/ja910769j.

Abstract

We describe a 12-step enantioselective synthetic route to the complex anticancer antimicrobial agent kinamycin F (3). Key to the success of the route was the development of a three-step sequence for construction of the diazonapthoquinone (diazofluorene, blue in structure 3) function of the natural product. This sequence comprises fluoride-mediated coupling of a beta-(trimethylsilylmethyl)-cyclohexenone and halonapthoquinone, palladium-mediated cyclization to construct the tetracyclic scaffold of the natural product, and mild diazo-transfer to a complex cyclopentadiene to introduce the diazo function. Ortho-quinone methide intermediates, formed by reduction and loss of dinitrogen from 3, have been postulated to form in vivo, and our approach provides a straightforward synthetic pathway to such compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / chemical synthesis*
  • Quinones / chemical synthesis
  • Stereoisomerism

Substances

  • Antibiotics, Antineoplastic
  • Quinones
  • kinamycin F