印楝素类柠檬苦素化合物ABD核心骨架的快速合成

doi:10.6023/cjoc202204048

有机化学 ›› 2022, Vol. 42 ›› Issue (9): 2857-2866.DOI: 10.6023/cjoc202204048 上一篇下一篇

研究论文

印楝素类柠檬苦素化合物ABD核心骨架的快速合成

董长明^a, 谢熠^a, 梁广鑫^a^,^b^,^*()

a 南开大学化学学院元素有机化学国家重点实验室天津 300071
b 上海科技大学物质科学与技术学院上海201210

收稿日期:2022-04-18 修回日期:2022-05-31 发布日期:2022-06-16
通讯作者: 梁广鑫
基金资助:
国家重点研发计划(2017YFD0201404); 国家自然科学基金(21772097); 国家自然科学基金(21572104)

A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids

Changming Dong^a, Yi Xie^a, Guangxin Liang^a^,^b()

a State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071
b School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210

Received:2022-04-18 Revised:2022-05-31 Published:2022-06-16
Contact: Guangxin Liang
Supported by:
National Key Research and Development Program of China(2017YFD0201404); National Natural Science Foundation of China(21772097); National Natural Science Foundation of China(21572104)

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摘要/Abstract

为实现印楝素类柠檬苦素及其类似物的快速合成, 报道了从香芹酮出发, 高立体选择性地合成印楝素ABD三环母核结构的方法. 合成路线的亮点是通过分子内的乙腈氧化物-烯烃环加成反应, 以很好的立体选择性实现反式十氢萘环体系的快速构建. 接下来通过Sonogashira偶联、异噁唑啉开环、甲磺酰化及分子内的S_N2取代等一系列简单高效的反应, 实现了印楝素三环骨架的规模合成, 总路线共13步, 总收率6.1%. 该中间体可以作为合成印楝素及其类似物的高官能团化左翼片段, 与目前方法相比, 此方法操作简便, 易于实现, 为实现该类天然产物的合成奠定了基础.

关键词: 印楝素, 柠檬苦素, 反式十氢萘环, 分子内乙腈氧化物-烯烃环加成(INOC)反应, 异噁唑啉

In an effort to rapidly construct the azadirachtin-type limonoids and analogues, a highly diastereoselective synthesis of the ABD tricyclic core in azadirachtin-type limonoids from (–)-carvone has been developed. The synthetic avenue features an intramolecular nitrile oxide-alkene cycloaddition (INOC) reaction to assemble the trans-decalin system in highly stereoselective manner. By further utilizing an efficient sequence of Sonogashira coupling, isoxazoline reduction, stereocontrolled dihydroxylation, mesylation and intramolecular S_N2 substitution, a scalable stereoselective synthesis of the tricyclic core skeleton of azadirachtin in 13 linear steps was achieved with 6.1% total yield. This intermediate can serve as a highly functionalized left-wing fragment for the synthesis of azadirachtin and its analogues. Compared with existing methods, the methods reported herein are simple, reliable, easy to implement, and significantly advances research on the synthesis of the azadirachtin-type limonoids.

Key words: azadirachtin, limonoids, trans-decalin, intramolecular nitrile oxide-alkene cycloaddition (INOC) reaction, isoxazoline

引用此文

董长明, 谢熠, 梁广鑫. 印楝素类柠檬苦素化合物ABD核心骨架的快速合成[J]. 有机化学, 2022, 42(9): 2857-2866.

Changming Dong, Yi Xie, Guangxin Liang. A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids[J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2857-2866.

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图/表 5

Scheme 1. Selected syntheses of left-wing fragment of azadirachtin

Scheme 2. Retrosynthtic analysis of azadirachtin

Scheme 3. Construction of trans-decalin 2

Scheme 4. Construction of enol triflate tricyclic core

Scheme 5. Construction of alkyne tricyclic core

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印楝素类柠檬苦素化合物ABD核心骨架的快速合成

A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids

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