School of Pharmaceutical Sciences, MOE Key Laboratory of, Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, 100084, China.
Angew Chem Int Ed Engl. 2021 Jun 21;60(26):14545-14553. doi: 10.1002/anie.202102614. Epub 2021 May 26.
The collective synthesis of skeletally diverse Stemona alkaloids featuring tailored dyotropic rearrangements of β-lactones as key elements is described. Specifically, three typical 5/7/5 tricyclic skeletons associated with stemoamide, tuberostemospiroline and parvistemonine were first accessed through chemoselective dyotropic rearrangements of β-lactones involving alkyl, hydrogen, and aryl migration, respectively. By the rational manipulation of substrate structures and reaction conditions, these dyotropic rearrangements proceeded with excellent efficiency, good chemoselectivity and high stereospecificity. Furthermore, several polycyclic Stemona alkaloids, including saxorumamide, isosaxorumamide, stemonine and bisdehydroneostemoninine, were obtained from the aforementioned tricyclic skeletons through late-stage derivatizations. A novel visible-light photoredox-catalyzed formal [3+2] cycloaddition was also developed, which offers a valuable tool for accessing oxaspirobutenolide and related scaffolds.
描述了一种具有独特骨架多样性的斯替诺生物碱的集体合成方法，其关键元素是β-内酰胺的定制双稠合重排。具体来说，首次通过涉及烷基、氢和芳基迁移的β-内酰胺的化学选择性双稠合重排，分别获得了与斯替诺酰胺、块茎螺环碱和帕维司莫宁相关的三种典型的 5/7/5 三环骨架。通过合理地操纵底物结构和反应条件，这些双稠合重排具有优异的效率、良好的化学选择性和高立体特异性。此外，通过上述三环骨架的后期衍生化，得到了几种多环斯替诺生物碱，包括沙索罗酰胺、异沙索罗酰胺、斯替诺宁和双去氢新斯替诺宁碱。还开发了一种新颖的可见光光氧化还原催化的形式[3+2]环加成反应，为获得噁唑螺戊烯内酯和相关支架提供了一种有价值的工具。
