Scalable Total Synthesis of (+)- and (-)-Codonopiloneolignanin A via Ti(IV)/NHC Cooperative Control Highly Enantioselective Dimerization of Multisubstituted Cinnamaldehyde.
Scalable Total Synthesis of (+)- and (-)-Codonopiloneolignanin A via Ti(IV)/NHC Cooperative Control Highly Enantioselective Dimerization of Multisubstituted Cinnamaldehyde.
复制标题
通过 Ti(IV)/NHC 协同控制多取代肉桂醛的高对映选择性二聚化可大规模全合成 ( )- 和 (-)-Codonopilone 木脂素 A。
DOI：
10.1021/acs.orglett.1c02408
复制
发表时间：
2021-07
期刊：
影响因子：
5.2
通讯作者：
Xie Zhixiang
中科院分区：
文献类型：
--
作者：
Li Xiangxin;Yong Huaya;Fan Xiaohong;Zheng Yajuan;Wang Zhen;Xie Zhixiang
以多取代肉桂醛为起始原料，经四步反应首次实现了（+）-和（-）-codonopiloneolignanin A的克级不对称全合成，总收率37%。通过多取代肉桂醛的高度对映选择性二聚反应，然后进行一系列级联反应（包括Prins环化、阳离子介导的环化和脱保护），有效构建了具有合成挑战性的三环[5，3，0，03，8]癸烷骨架。此外，NHC催化/Ti（IV）介导的协同控制多取代肉桂醛二聚反应的范围进行了研究。值得注意的是，测试了Codonopiloneolignanin A及其对映异构体（在自然界中特别稀缺）的生物活性，并显示出良好的抗癌活性。
The first gram-scale asymmetric total synthesis of (+)- and (-)-codonopiloneolignanin A has been achieved from multisubstituted cinnamaldehyde in four steps with 37% overall yield. The synthetically challenging tricyclic [5, 3, 0, 03,8] decane skeleton was efficiently constructed via a highly enantioselective dimerization of multisubstituted cinnamaldehyde, followed by a sequence of cascade reactions including Prins cyclization, cation mediated cyclization, and deprotection. Furthermore, the scope of NHC-catalyzed/Ti(IV)-mediated synergistic control multisubstituted cinnamaldehyde dimerization was investigated. Significantly, the bioactivity of codonopiloneolignanin A and its enantiomer, particularly scarce in nature, was tested and showed good anticancer activity.