抗血管生成天然产物Penduliflaworosin的不对称全合成及结构修正
收稿日期: 2024-09-20
修回日期: 2024-10-31
网络出版日期: 2024-12-06
基金资助
国家自然科学基金(22071030); 国家自然科学基金(22222104); 上海市科学技术委员会(22JC1401102)
Asymmetric Total Synthesis and Structural Revision of Antiangiogenic Natural Product Penduliflaworosin
Received date: 2024-09-20
Revised date: 2024-10-31
Online published: 2024-12-06
Supported by
National Natural Science Foundation of China(22071030); National Natural Science Foundation of China(22222104); Science and Technology Commission of Shanghai Municipality(22JC1401102)
Penduliflaworosin是一种从药用植物鸡骨香(Croton crassifolius)中分离得到的二萜天然产物, 具有很强的抗血管生成作用. 在本工作中, 首次实现了penduliflaworosin及其C4差向异构体的不对称全合成, 修正了文献中关于penduli- flaworosin的常用错误结构. 在该合成路线中, 利用2-吡喃酮与多取代1,4-环己二烯的烯烃异构/不对称反电子需求Diels-Alder反应, 高效构建了含有两个全碳季碳手性中心的顺式氢化萘母核骨架, 并通过3-呋喃基锌的1,2-加成反应、氧化、烯烃异构化等关键反应, 完成了该天然产物及其差向异构体的不对称全合成.
斯绪格 , 蔡泉 . 抗血管生成天然产物Penduliflaworosin的不对称全合成及结构修正[J]. 有机化学, 2025 , 45(3) : 959 -968 . DOI: 10.6023/cjoc202409025
Penduliflaworosin is a diterpenoid natural product isolated from the medicinal plant Croton crassifolius, which demonstrates highly potent antiangiogenic activities. In this work, enantioselective total synthesis of penduliflaworosin and its C4 epimer has been realized for the first time, thus revising the erroneous structure of penduliflaworosin shown in previous literatures. In the synthesis, the main cis-decalin moiety bearing two quaternary stereogenic centers was efficiently constructed by tandem olefin migration/asymmetric inverse-electron-demand Diels-Alder reaction of 2-pyrone with polysubstituted 1,4- cyclohexadiene. From this intermediate, enantioselective synthesis of penduliflaworosin and its epimer was realized by subsequent several key steps, involving the 1,2-addition with 3-furanyl zinc reagent, oxidation, and olefin isomerization.
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