Total Synthesis of Longeracinphyllin A

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.

首次成功实现了六环大叶吊兰生物碱长叶吊兰苷A的非对称全合成。通过银催化的炔烃环化和卢奇自由基环化反应，制备了四环中间体。利用膦促进的[3+2]环加成反应，构建了具有邻近三级和四级中心的立体拥挤的E环。通过分子内霍纳-沃茨-埃蒙斯烯化反应，组装了环戊酮基团。在后期阶段，通过雷尼镍还原从硫酰胺前体中得到了三级胺。