Synthetic Studies on Lyconadin A and related compounds

完成了石蒜属生物碱lyconadin A的全合成，并将其应用于相关同源物lyconadin B和c的全合成。lyconadin A由于其前所未有的五环骨架而成为全合成的一个具有挑战性的靶点。我们合成的lyconadin A的特点是通过aza-Prins反应和电环开环结合，然后形成C-N键，轻松构建高度融合的四环骨架。广泛研究了四环上溴烯烃部分转化为关键烯酮中间体的方法，并建立了通过硫化物、肟或叠氮化物中间体的三种方法。由关键烯酮中间体构建一个吡啶酮环，完成了lyconadin A的合成。同样的烯酮中间体也可以形成一个二氢吡啶酮环，从而合成了lyconadin b。

The total synthesis of the Lycopodium alkaloid lyconadin A was accomplished and it was applied to the total syntheses of the related congeners, lyconadins B and C. Lyconadin A has attracted attention as a challenging target for total synthesis due to the unprecedented pentacyclic skeleton. Our synthesis of lyconadin A features a facile construction of the highly fused tetracyclic skeleton through a combination of an aza-Prins reaction and an electrocyclic ring opening, followed by formation of a C-N bond. Transformation of the bromoalkene moiety of the tetracycle to a key enone intermediate was extensively investigated, and three methods via sulfide, oxime, or azide intermediates were established. A pyridone ring was constructed from the key enone intermediate to complete the synthesis of lyconadin A. A dihydropyridone ring could also be formed from the same enone intermediate, leading to a synthesis of lyconadin B. Establishment of the conditions for an electrocyclic ring opening without formation of the C-N bond resulted in completion of the total synthesis of lyconadin C.