Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St, Cambridge, MA, 02138, USA.
Chemistry. 2021 Aug 2;27(43):11126-11131. doi: 10.1002/chem.202100975. Epub 2021 May 27.
The family of anti-fungal natural products known as the ambruticins are structurally distinguished by a pair of pyran rings adorning a divinylcyclopropane core. Previous characterization of their biosynthesis, including the expression of a genetically modified producing organism, revealed that the polyketide synthase pathway proceeds via a diol intermediate, known as ambruticin J. Herein, we report the first enantioselective total synthesis of the putative PKS product, ambruticin J, according to a triply convergent synthetic route featuring a Suzuki-Miyaura cross-coupling and a Julia-Kocienski olefination for fragment assembly. This synthesis takes advantage of synthetic methodology previously developed by our laboratory for the stereoselective generation of the trisubstituted cyclopropyl linchpin.
已知的抗真菌天然产物家族被称为 amb 菌素，其结构的特点是一对吡喃环装饰在一个二乙烯基环丙烷核心上。以前对其生物合成的表征，包括表达遗传修饰的产生生物体，表明聚酮合酶途径通过二醇中间体进行，称为 amb 菌素 J。在此，我们根据具有 Suzuki-Miyaura 交叉偶联和 Julia-Kocienski 烯烃化的三重收敛合成路线，报道了第一个对映选择性全合成假定的 PKS 产物 amb 菌素 J 的报道。该合成利用了我们实验室以前开发的立体选择性生成三取代环丙基关键中间体的合成方法。
