Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Nat Chem. 2017 Oct;9(10):944-949. doi: 10.1038/nchem.2801. Epub 2017 Jun 19.
Tubingensin B is an indole diterpenoid that bears a daunting chemical structure featuring a disubstituted carbazole unit, five stereogenic centres-three of which are quaternary-and a decorated [3.2.2]-bridged bicycle. We describe our synthetic design toward a concise and enantiospecific total synthesis of tubingensin B, which hinges on the strategic use of a transient aryne intermediate. Although initial studies led to unexpected reaction outcomes, we ultimately implemented a sequence of carbazolyne cyclization followed by Rh-catalysed fragmentation to install the seven-membered ring and vicinal quaternary stereocentres of the natural product. Coupled with a late-stage radical cyclization to construct the [3.2.2]-bridged bicycle, these efforts have enabled the total synthesis of tubingensin B. The design and evolution of our succinct total synthesis underscores the utility of long-avoided aryne intermediates for the introduction of structural motifs that have conventionally been viewed as challenging.
tubingensin B 是一种吲哚二萜类化合物，具有令人望而生畏的化学结构，其中包含一个取代的咔唑单元、五个立体中心——其中三个是季碳原子——以及一个装饰性的[3.2.2]-桥接自行车。我们描述了我们对 tubingensin B 的简洁和对映选择性全合成的合成设计，这取决于对瞬态芳炔中间体的战略使用。尽管最初的研究导致了意外的反应结果，但我们最终实施了一系列 carbazolyne 环化反应，随后进行 Rh 催化的断裂，以安装天然产物的七元环和相邻的季立体中心。与后期的自由基环化反应相结合，构建[3.2.2]-桥接自行车，这些努力实现了 tubingensin B 的全合成。我们简洁全合成的设计和演变突出了长期回避的芳炔中间体在引入传统上被认为具有挑战性的结构基序方面的实用性。
