Cryptoquinonemethides合成中螺五环非对映异构体环丙烷化反应活性及选择性研究

doi:10.6023/cjoc202508010

有机化学 ›› 2026, Vol. 46 ›› Issue (1): 96-105.DOI: 10.6023/cjoc202508010 上一篇下一篇

研究论文

Cryptoquinonemethides合成中螺五环非对映异构体环丙烷化反应活性及选择性研究

张元贺^a^,^b, 沈运杰^a^,^b, 谈东兴^a^,^*(), 韩福社^a^,^b^,^*()

^a 中国科学院长春应用化学研究所绿色化学与过程吉林省重点实验室长春 130022
^b 中国科学技术大学应用化学与工程学院合肥 230026

收稿日期:2025-08-07 修回日期:2025-09-05 发布日期:2025-09-17
基金资助:
国家自然科学基金(22471261); 国家自然科学基金(22071235)

Study on the Cyclopropanation Reactivity and Selectivity of Spiroannulated Pentacyclic Diastereoisomers toward Synthesizing Cryptoquinonemethides

Yuanhe Zhang^a^,^b, Yunjie Shen^a^,^b, Dongxing Tan^a^,^*(), Fushe Han^a^,^b^,^*()

^a Jilin Province Key Lab of Green Chemistry and Process, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022
^b School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026

Received:2025-08-07 Revised:2025-09-05 Published:2025-09-17
Contact: * E-mail: dxtan@ciac.ac.cn; fshan@ciac.ac.cn
Supported by:
National Natural Science Foundation of China(22471261); National Natural Science Foundation of China(22071235)

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摘要/Abstract

6-6-6-5-5螺五环化合物是本课题组发展的合成含亚甲基苯醌结构的C30萜类天然物及其立体异构体路线中的关键中间体, 几种非对映异构体的立体构型对后期环丙烷化反应的活性和立体选择性有显著影响. 对几种非对映异构体构型影响环丙烷化反应活性和立体选择性的原因进行了详细探究. 首先通过适当的衍生化, 并结合二维核磁分析确定了四个非对映异构体中C9, C8和C14的构型, 据此将异构体的构型与反应活性和选择性一一对应. 随后根据确定的构型, 利用密度泛函(DFT)理论计算对四个异构体的三维结构进行了优化, 从立体效应的角度为解释异构体之间存在反应活性和选择性差异的原因提供了直观证据. 此外, 还利用氘代实验对构建6-6-6-5-5螺并环骨架的分子内Michael/ aldol串联反应的机理进行了探究.

关键词: 环丙烷化, 螺五环非对映异构体, 密度泛函理论计算, Michael/aldol串联反应

A detailed investigation was carried out to understand how the variations in configurations of the spiroannulated 6-6-6-5-5 pentacyclic diastereoisomers, the key intermediates for the synthesis of two C30 terpene quinonemethides and their stereoisomers, impact the reactivity of cyclopropanation. The configurations at C9, C8, and C14 for all four pentacyclic diastereoisomers involved in the diastereoisomeric mixture were determined through a combination of suitable chemical derivatization and multiple NMR spectroscopic analyses. Based on the defined configuration, the 3D structures of these diastereoisomers were optimized by density functional theory (DFT) calculation. These investigations provide reasonable supports, mainly from the steric considerations, for understanding why different diastereoisomers exhibit markedly different reactivity, as well as regio- and stereo-selectivity for cyclopropanation. In addition, the mechanism for the construction of the spiroannulated 6-6-6-5-5 pentacyclic scaffold via intramolecular Michael/aldol cascade was also investigated by deuterium labeling experiments.

Key words: cyclopropanation, spiroannulated pentacyclic diastereoisomers, density functional theory (DFT) calculation, Michael/aldol cascade

引用此文

张元贺, 沈运杰, 谈东兴, 韩福社. Cryptoquinonemethides合成中螺五环非对映异构体环丙烷化反应活性及选择性研究[J]. 有机化学, 2026, 46(1): 96-105.

Yuanhe Zhang, Yunjie Shen, Dongxing Tan, Fushe Han. Study on the Cyclopropanation Reactivity and Selectivity of Spiroannulated Pentacyclic Diastereoisomers toward Synthesizing Cryptoquinonemethides[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 96-105.

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图/表 5

Scheme 1. Proposed biogenetic pathway (A) and our synthetic route for chamaecydin (B)

Scheme 2. Isomerization mechanism of E-7 to Z-7

Scheme 3. Assignment of the absolute configuration of pentacyclic compound 8

Scheme 4. Assignment of the absolute configuration of pentacyclic compound 15

Figure 1. Optimized 3D structures

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Cryptoquinonemethides合成中螺五环非对映异构体环丙烷化反应活性及选择性研究

Study on the Cyclopropanation Reactivity and Selectivity of Spiroannulated Pentacyclic Diastereoisomers toward Synthesizing Cryptoquinonemethides

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