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

doi:10.6023/cjoc202508010

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (1): 96-105.DOI: 10.6023/cjoc202508010 Previous Articles Next Articles

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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

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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Abstract

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

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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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Fig. & Tab. 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

References 23

[1]	Hirose Y.; Hasegawa S.; Ozaki N. Tetrahedron 1983, 24, 1535.
[2]	Shibuya T. Phytochemistry 1992, 31, 4289. doi: 10.1016/0031-9422(92)80460-V
[3]	Su W.-C.; Fang J.-M.; Cheng Y.-S. Phytochemistry 1993, 34, 779. doi: 10.1016/0031-9422(93)85358-X
[4]	Fukushima J.-I.; Yatagai M.; Ohira T. J. Wood Sci. 2002, 48, 326. doi: 10.1007/BF00831355
[5]	Chen C.-C.; Wu J.-H.; Yang N.-S.; Chang J.-Y.; Kuo C.-C.; Wang S.-Y.; Kuo Y.-H. Org. Lett. 2010, 12, 2786. doi: 10.1021/ol1009027
[6]	Lyu M.-Y.; Zhong Z.; Lo V. K.-Y.; Wong H. N. C.; Peng X.-S. Angew. Chem., Int. Ed. 2020, 59, 19929. doi: 10.1002/anie.v59.45
[7]	Huang Y.; Zhang J.; Pettus T. R. R. Org. Lett. 2005, 7, 5841. doi: 10.1021/ol0523749
[8]	Fürstner A. Chem. Soc. Rev. 2009, 38, 3208. doi: 10.1039/b816696j pmid: 19847352
[9]	Godeau J.; Olivero S.; Antoniotti S.; Duñach E. Org. Lett. 2011, 13, 3320. doi: 10.1021/ol201028f
[10]	Zhang X.; Tan X.; Duan S.; Chi Z.; Liu S.; Xie Z. Org. Lett. 2023, 25, 7769. doi: 10.1021/acs.orglett.3c02483
[11]	Chai Y.; Hong S.-P.; Lindsay H. A.; McFarland C.; McIntosh M. C. Tetrahedron 2002, 58, 2905. doi: 10.1016/S0040-4020(02)00164-3
[12]	Zhang Y.-H.; Deng L.-H.; Tan D.-X.; Han F.-S. Angew. Chem., Int. Ed. 2025, 64, e202423944.
[13]	Chen S.; Rong C.; Feng P.; Li S.; Shi Y. Org. Biomol. Chem. 2012, 10, 5518. doi: 10.1039/c2ob25923k
[14]	Hu N.; Liang J.-T.; Xie Y.-B.; Li C.-C.; He Y.-T.; Hu Y.-J. Eur. J. Org. Chem. 2025, 28, e202500399.
[15]	Simmons H. E.; Cairns T. L.; Vladuchick S. A.; Hoiness C. M. Org. React. 1973, 20, 1.
[16]	Lebel H.; Marcoux J.-F.; Molinaro C.; Charette A. B. Chem. Rev. 2003, 103, 977. doi: 10.1021/cr010007e
[17]	Furukawa J.; Kawabata N.; Nishimura J. Tetrahedron Lett. 1966, 7, 3353. doi: 10.1016/S0040-4039(01)82791-X
[18]	Yang Z.; Lorenz J. C.; Shi Y. Tetrahedron Lett. 1998, 39, 8621. doi: 10.1016/S0040-4039(98)01954-6
[19]	Bank S.; Rowe Jr C. A.; Schriesheim A.; Naslund L. A. J. Org. Chem. 1968, 33, 221. doi: 10.1021/jo01265a042
[20]	Dauben W. G.; Michno D. M. J. Org. Chem. 1977, 42, 682. doi: 10.1021/jo00424a023
[21]	Michalak K.; Michalak M.; Wicha J. Tetrahedron Lett. 2008, 49, 6807. doi: 10.1016/j.tetlet.2008.09.082
[22]	Wang C.; Wang D.; Gao S.-H. Org. Lett. 2013, 15, 4402. doi: 10.1021/ol4019425
[23]	Yusubov M. S.; Chi K.-W.; Park J. Y.; Karimovc R.; Zhdankin V. V. Tetrahedron Lett. 2006, 47, 6305.

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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