Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
J Am Chem Soc. 2010 Mar 3;132(8):2540-1. 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.
我们描述了一种 12 步对映选择性合成复杂抗癌抗生素金霉素 F（3）的方法。该路线成功的关键是开发了三步序列，用于构建天然产物的重氮萘醌（重氮芴，结构 3 中的蓝色部分）功能。该序列包括氟介导的β-（三甲基甲硅烷基甲基）-环己烯酮和卤萘醌的偶联、钯介导的环化以构建天然产物的四环支架，以及温和的重氮转移到复杂的环戊二烯以引入重氮功能。由 3 还原和失去二氮形成的邻醌甲叉中间体已被假定在体内形成，我们的方法为这类化合物提供了一条直接的合成途径。
