Development of a Convergent Entry to the Diazofluorene Antitumor Antibiotics: Enantioselective Synthesis of Kinamycin F

作者：Woo Christina M; Lu Liang; Gholap Shivajirao L; Smith Devin R; Herzon Seth B^*

来源：Journal of the American Chemical Society, 2010, 132(8): 2540-+.

DOI：10.1021/ja910769j

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.

• 出版日期2010-3-3