State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University , 222 Tianshui Nanlu, Lanzhou 730000, China.
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
J Am Chem Soc. 2017 Mar 29;139(12):4282-4285. doi: 10.1021/jacs.6b13401. Epub 2017 Mar 10.
The first total syntheses of Lycopodium alkaloids palhinine A, palhinine D, and their C3-epimers have been divergently achieved through the use of a connective transform to access a pivotal hexacyclic isoxazolidine precursor. A microwave-assisted regio- and stereoselective intramolecular nitrone-alkene cycloaddition was tactically orchestrated as a key step to install the crucial 10-oxa-1-azabicyclo[5.2.1]decane moiety embedded in the conformationally rigid isotwistane framework, demonstrating the feasibility of constructing the highly strained medium-sized ring by introduction of an oxygen bridging linker to relieve the transannular strain in the polycyclic scaffold. Subsequent N-O bond cleavage provided the synthetically challenging nine-membered azonane ring system bearing the requisite C3 hydroxyl group. Late-stage transformations featuring a chemo- and stereoselective reduction of the pentacyclic β-diketone secured the availability of our target molecules.
通过使用连接变换来获得关键的六元环异噁唑烷前体，实现了石松生物碱 palhinine A、palhinine D 及其 C3-差向异构体的首次全合成。微波辅助区域和立体选择性的分子内硝酮-烯烃环加成被巧妙地设计为关键步骤，以安装在构象刚性的异扭烷骨架中嵌入的关键 10-氧代-1-氮杂双环[5.2.1]癸烷部分，证明了通过引入氧桥连键来构建高度应变的中环以缓解多环支架中环间应变的可行性。随后的 N-O 键断裂提供了具有所需 C3 羟基的合成上具有挑战性的九元氮杂烷环系统。具有化学和立体选择性还原的后期转化特征，确保了目标分子的可用性。
