State Key Laboratory of Chemical Oncogenomics and Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Shenzhen Bay Laboratory, Shenzhen 518055, China.
Org Lett. 2021 Jun 4;23(11):4088-4093. doi: 10.1021/acs.orglett.1c00769. Epub 2021 May 14.
The structurally intriguing tetracyclic core of complex harziane diterpenoid was constructed in 14 steps from commercially available 3-ethoxycyclohex-2-en-1-one. The key steps were a Mn/Cu-mediated oxidative 1,3-dicarbonyl radical cascade cyclization reaction, which diastereoselectively formed the core of dimethylbicyclo[3.2.1]octane structure, and a Au-catalyzed diastereoselective formal [2 + 2] cycloaddition for construction of the harziane diterpenoid tetracyclic framework. The developed method paves the way for achieving total synthesis of this type of complex natural product.
从商业可得的 3-乙氧基环己-2-烯-1-酮出发，经 14 步反应以高非对映选择性构建了结构独特的含四环稠合海松烷二萜核心骨架。关键步骤包括：Mn/Cu 介导的氧化 1,3-二羰基自由基级联环化反应，立体选择性地形成了二甲基二环[3.2.1]辛烷结构的核心；以及 Au 催化的非对映选择性形式[2 + 2]环加成反应，构建了海松烷二萜的四环骨架。所开发的方法为实现此类复杂天然产物的全合成铺平了道路。
