基于Catellani策略不对称合成quinocarcin家族生物碱

Quinocarcin家族是一类重要的四氢异喹啉生物碱，主要成员有(-)-quinocarcin、(-)-tetrazomine和(-)-lemonomycin。它们都表现出良好的抗肿瘤和抗菌活性，是新药研发的重要先导化合物。在分子结构上看，这类天然产物具有较为复杂的多环结构，其中包含1,3-顺式四氢异喹啉和双氮杂[3,2,1]-桥环结构。这些独特的复杂环系结构给这类天然产物的全合成带来了很大的挑战。自上世纪80年代以来，已有多个课题组完成了本家族成员的合成，但由于对核心的1,3-顺式四氢异喹啉单元的构筑缺乏高效的合成方法，整体合成效率上仍有较大的提升空间。我们小组近期发展了通过Catellani策略一步构建1,3-顺式四氢异喹啉的新方法。基于此方法，我们设计了以简单的有机试剂为原料合成quinocarcin家族成员的通用策略，有望显著提高合成效率。

The quinocarcins belong to an important subfamily of tetrahydroisoquinoline (THIQ) alkaloids. (-)-Quinocarcin, (-)-tetrazomine and (-)-lemonomycin are typical members of this family. They show good anti-tumor and antibiotic activities, therefore becoming important leads for drug discovery. Structurally, these molecules possess complex polycyclic skeletons, which include 1,3-cis- tetrahydroisoquinoline, piperazine and pyrrolidine motifs. These structure features bring along big challengs for their total synthesis. Since 1980s, several groups have finished the total synthesis of quinocarcins. However, there is still big room for improvement regarding the synthetic efficiency, especially for the assembly of the core 1,3-cis- tetrahydroisoquinoline motif. Our group recently developed a one-step protocol for the synthesis of 1,3-cis- tetrahydroisoquinolines through the Catellani reaction. Based on this method, we design a general strategy for the synthesis of quinocarcins from simple starting materials, which will significantly increase the synthetic efficiency.