Department of Chemistry, The Hong Kong University of Science and Technology , Clearwater Bay, Kowloon, Hong Kong, China.
Org Lett. 2014 Jun 6;16(11):2986-9. doi: 10.1021/ol501120m. Epub 2014 May 12.
The first, asymmetric total syntheses of potent antimicrobial Psoracorylifol B (>1.3 g obtained, dr 10.5:1) with a 9.4% overall yield on a gram scale in 14 steps and ent-Psoracorylifol C with a 4.3% yield in 16 steps were achieved. The key features of our synthesis include (i) sequential, rarely explored Achmatowicz rearrangement/bicycloketalization to construct the 6,8-dioxabicyclo[3.2.1]octane core, and (ii) Cu-mediated SN2' methylation or Johnson-Claisen rearrangement to stereoselectively install the all-carbon quaternary stereocenter. This concise, highly efficient, and scalable synthetic route may provide expedited and practical access to psoracorylifols and their analogues for further biological activity evaluation.
首次以克级规模（14 步总收率 9.4%，dr 10.5:1，获得 1.3 克以上产物）不对称全合成了具有强抗菌活性的 Psoracorylifol B 和 ent-Psoracorylifol C，总收率分别为 4.3%和 16 步。我们的合成关键特点包括：（i）连续、很少探索的 Achmatowicz 重排/双环缩酮化反应构建 6,8-二氧杂双环[3.2.1]辛烷核心；（ii）Cu 介导的 SN2' 甲基化或 Johnson-Claisen 重排反应，立体选择性地构建全碳季碳中心。这种简洁、高效和可规模化的合成路线可能为 psoracorylifols 及其类似物的进一步生物活性评价提供快速、实用的途径。
