Department of Chemistry, University of California, Berkeley, CA, USA.
Nat Chem. 2022 Apr;14(4):450-456. doi: 10.1038/s41557-021-00870-4. Epub 2022 Feb 14.
Natural product total synthesis inspires the development of synthesis strategies to access important classes of molecules. In the 1960s, Corey and coworkers demonstrated a visionary preparation of the terpenoid longifolene, using 'strategic bond analysis' to craft a synthesis route. This approach proposes that efficient synthesis routes to bridged, polycyclic structures should be formulated to introduce the bulk of the target's topological complexity at a late stage. Subsequently, similar strategies have proved general for the syntheses of a wide variety of bridged, polycyclic molecules. Here, we demonstrate that an orthogonal strategy where topological complexity is introduced at the outset leads to the short synthesis of the longifolene-related terpenoid longiborneol. To implement this strategy, we access a bicyclo[2.2.1] starting material through scaffold remodelling of readily available (S)-carvone. We also employ a variety of late-stage C-H functionalization tactics in divergent syntheses of many longiborneol congeners. Our strategy may prove effective for the preparation of other topologically complex natural products that contain the bicyclo[2.2.1] framework.
天然产物全合成激发了合成策略的发展,以获取重要类别的分子。20 世纪 60 年代,Corey 及其同事展示了萜类化合物长叶烯的有远见的制备方法,使用“战略键分析”来构建合成路线。该方法提出,对于桥连、多环结构的有效合成路线,应该在后期引入目标拓扑复杂性的大部分。随后,类似的策略已被证明适用于广泛的桥连、多环分子的合成。在这里,我们证明了一种正交策略,其中在开始时引入拓扑复杂性可以导致相关萜类化合物长叶烯醇的短合成。为了实施该策略,我们通过 readily available (S)-carvone 的支架重塑来获得双环[2.2.1]起始原料。我们还在许多长叶烯同系物的发散合成中采用了各种后期 C-H 官能团化策略。我们的策略可能对制备其他包含双环[2.2.1]骨架的拓扑复杂天然产物有效。