Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D.
Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D.
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DOI：
10.1021/jacs.7b10135
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发表时间：
2018-02
影响因子：
15
通讯作者：
Jin-Xin Zhao;Yan-yan Yu;Sha-Sha Wang-Sha;Suling Huang;Yu Shen;Xin-Hua Gao;Li Sheng;Jing-Ya Li
中科院分区：
文献类型：
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作者：
Jin-Xin Zhao;Yan-yan Yu;Sha-Sha Wang-Sha;Suling Huang;Yu Shen;Xin-Hua Gao;Li Sheng;Jing-Ya Li
Hongkoxylum A-D（1-4）是从香港八角木（Dysoxylum hongkongense）中分离得到的第一个抗坏血酸化萜类化合物，具有独特的5，5，5-稠合三环螺酮缩丁内酯结构和二萜衍生的长链。通过光谱数据、化学降解、X射线晶体学、CD分析和全合成的组合，明确地指定了它们的结构。化合物1-4的全合成有效地通过收敛策略完成，其中最长的线性序列为12- 1 - 4步，总收率为5.4- 9.6%。值得注意的是，我们利用了一种生物启发的一锅法，通过涉及精心设计的克莱森重排，脱保护和5-外消旋环化的级联反应，从容易制备的化合物12构建关键中间体14。然后将所需的主要差向异构体14 a转化为主要结构单元21。通过NHK偶联反应进行21和长链乙烯基碘7的组装以提供1-4的骨架。一些hongkorin和/或合成类似物显示出对NF-κB、11β-HSD 1和甾醇合成的显著至中度抑制活性。活性最高的NF-κB抑制剂34对RAW 246.7和原代BMDM细胞中LPS诱导的炎症反应表现出明显的抑制作用。
Hongkonoids A-D (1-4), the first example of ascorbylated terpenoids featuring a unique 5,5,5-fused tricyclic spiroketal butyrolactone moiety and diterpenoid-derived long chain, were isolated from Dysoxylum hongkongense. Their structures were unambiguously assigned by a combination of spectroscopic data, chemical degradation, X-ray crystallography, CD analysis, and total synthesis. The total syntheses of compounds 1-4 were effectively accomplished by a convergent strategy with the longest linear sequences of 12-14 steps and overall yields of 5.4-9.6%. Notably, we exploited a bioinspired one-pot method to construct the key intermediate 14 from an easily made compound 12 by involving the cascade reactions of an elaborate Claisen rearrangement, deprotections, and a 5-exo-trig cyclization. The desired major epimer 14a was then transformed to the main building block 21. Assembly of 21 and the long chain vinyl iodide 7 was made by an NHK coupling reaction to furnish the framework of 1-4. Some of the hongkonoids and/or synthetic analogs showed significant to moderate inhibitory activities against NF-κB, 11β-HSD1, and sterol synthesis. The most active NF-κB inhibitor 34 exhibited distinct inhibition on the LPS-induced inflammatory responses in RAW 246.7 and primary BMDM cells.