State Key Laboratory of Bioorganic and Natural Products Chemistry, Collaborative Innovation Center of Chemistry for Life Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, China.
J Am Chem Soc. 2017 Oct 25;139(42):14893-14896. doi: 10.1021/jacs.7b09186. Epub 2017 Oct 13.
The first and asymmetric total synthesis of longeracinphyllin A, a hexacyclic Daphniphyllum alkaloid, has been accomplished. A tetracyclic intermediate was prepared through silver-catalyzed alkyne cyclization and Luche radical cyclization. A phosphine-promoted [3 + 2] cycloaddition reaction was exploited to construct the sterically congested E ring bearing vicinal tertiary and quaternary centers. The cyclopentenone motif was assembled by using intramolecular Horner-Wadsworth-Emmons olefination. Raney Ni reduction delivered the tertiary amine from a thioamide precursor at a late stage.
首次完成了六元稠合的瑞香烷型生物碱 longeracinphyllin A 的不对称全合成。通过银催化的炔烃环化和 Luche 自由基环化反应制备了四环中间体。利用膦促进的[3+2]环加成反应构建了带有相邻三级和季碳中心的空间拥挤的 E 环。通过分子内 Horner-Wadsworth-Emmons 烯基化反应构建了环戊烯酮基序。在后期，Raney Ni 还原将硫代酰胺前体中的叔胺还原。
