Key Laboratory of Green Chemistry & Technology, of the Ministry of Education Institution, College of Chemistry, Sichuan University, Chengdu, Sichuan, 610064, China.
Chemistry. 2018 Jun 26;24(36):9120-9129. doi: 10.1002/chem.201801156. Epub 2018 Jun 6.
We report on our accomplishment of the asymmetric synthesis of hispidanin A and its natural precursor, a labdane diterpenoid. In the first generation of synthesis, a semi-synthesis strategy was employed to construct a labdane-type diterpenoid, a natural precursor of hispidanin A, in which Barton's photolytic remote functionalization was employed as a key transformation. In addition, the totarane-type dienophile counterpart was derived from commercially available (-)-scalareol. In the second generation of synthesis, key elements included an iron-catalyzed radical cascade to access the labdane-type diene on the basis of hydrogen atom transfer, and an enantioselective cationic polyene cyclization furnished the totarane-type dienophile. Reaction optimization and mechanistic analysis of the radical cascade reaction was conducted. Furthermore, the [4+2] cycloaddition reaction was achieved in excellent yield and selectivity under thermal conditions, which has been rationalized by using DFT transition-state analysis and paved the way for final accomplishment of the total synthesis of hispidanin A.
我们报告了（我们）实现了异土木蝴蝶素 A 及其天然前体，一种贝壳杉烷二萜的不对称合成。在第一代合成中，（我们）采用半合成策略构建了异土木蝴蝶素 A 的天然前体，贝壳杉烷二萜，其中 Barton 的光解远程官能化被用作关键转化。此外，从商业可得的(-)-贝壳杉醇衍生出了对映选择性的蒈烯型二烯。在第二代合成中，关键要素包括基于氢原子转移的铁催化自由基级联反应，以获得贝壳杉烷型二烯，以及对映选择性的阳离子多烯环化反应，以提供蒈烯型二烯。对自由基级联反应的优化和机理分析进行了研究。此外，在热条件下通过[4+2]环加成反应以优异的收率和选择性实现了该反应，通过 DFT 过渡态分析对其进行了合理化，并为最终实现异土木蝴蝶素 A 的全合成铺平了道路。
