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

ARTICLES

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
通讯作者: 谈东兴, 韩福社
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

Zhang Yuanhe^a^,^b, Shen Yunjie^a^,^b, Tan Dongxing^a^,^*(), Han Fushe^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: Tan Dongxing, Han Fushe
Supported by:
National Natural Science Foundation of China(22471261); National Natural Science Foundation of China(22071235)

1. .pdf(8295KB)

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

Cite this article

Zhang Yuanhe, Shen Yunjie, Tan Dongxing, Han Fushe. 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.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

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.
[3]	Su W.-C.; Fang J.-M.; Cheng Y.-S. Phytochemistry 1993, 34, 779.
[4]	Fukushima J.-I.; Yatagai M.; Ohira T. J. Wood Sci. 2002, 48, 326.
[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.
[6]	Lyu M.-Y.; Zhong Z.; Lo V. K.-Y.; Wong H. N. C.; Peng X.-S. Angew. Chem., Int. Ed. 2020, 59, 19929.
[7]	Huang Y.; Zhang J.; Pettus T. R. R. Org. Lett. 2005, 7, 5841.
[8]	Fürstner A. Chem. Soc. Rev. 2009, 38, 3208.
[9]	Godeau J.; Olivero S.; Antoniotti S.; Duñach E. Org. Lett. 2011, 13, 3320.
[10]	Zhang X.; Tan X.; Duan S.; Chi Z.; Liu S.; Xie Z. Org. Lett. 2023, 25, 7769.
[11]	Chai Y.; Hong S.-P.; Lindsay H. A.; McFarland C.; McIntosh M. C. Tetrahedron 2002, 58, 2905.
[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.
[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.
[17]	Furukawa J.; Kawabata N.; Nishimura J. Tetrahedron Lett. 1966, 7, 3353.
[18]	Yang Z.; Lorenz J. C.; Shi Y. Tetrahedron Lett. 1998, 39, 8621.
[19]	Bank S.; Rowe Jr C. A.; Schriesheim A.; Naslund L. A. J. Org. Chem. 1968, 33, 221.
[20]	Dauben W. G.; Michno D. M. J. Org. Chem. 1977, 42, 682.
[21]	Michalak K.; Michalak M.; Wicha J. Tetrahedron Lett. 2008, 49, 6807.
[22]	Wang C.; Wang D.; Gao S.-H. Org. Lett. 2013, 15, 4402.
[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

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 23

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Yuhan Zhao, Huimin Ma, Shulin Ge, Lingbin Kong. Iodine-Catalyzed Intermolecular Cyclopropanation of Olefins with Active Methylene Compounds [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3469-3477.
[2]	Xiaopeng Ling, Shaoping Tao, Qi Lin, Bingbing Shi, Hong Yao, Taibao Wei, Jinfa Chen. A Pillar[5]arene-Based π-Conjugated Dye Used for Fluorescence Sensing of L-Arginine [J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2480-2485.
[3]	Junqiang Jiao, Gaosheng Yang. Preparation of α-(Di(alkoxycarbonyl)methyl)chalcones and Their Application in the Synthesis of Multisubstituted Cyclopropanes [J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2586-2599.
[4]	Qinghao Sun, Xiaoguang Bao. Computational Insights into the Mechanism of the Mo-Catalyzed Deoxygenative Coupling of Aromatic Aldehydes [J]. Chinese Journal of Organic Chemistry, 2024, 44(11): 3518-3525.
[5]	Xuewei Chen, Fangcai Yu, Chuanhong Tian. 1,1'-Methylenediimidazolium-Based Multiple Hydrogen-Bond Donor Catalysts Facilitate the Cycloaddition of CO₂ with Epoxides under Atmospheric Pressure [J]. Chinese Journal of Organic Chemistry, 2024, 44(10): 3198-3205.
[6]	Wenlong Chen, Huimin Li, Pengfei Yang, Dongcheng Zheng, Gaosheng Yang. Reaction of 2-Aroylmethylenemalonates with Corey Ylide [J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1472-1482.
[7]	Man Xu, Yuanzhi Xia. Mechanistic Understanding of Rh(III)-Catalyzed Redox-Neutral C—H Activation/Annulation Reactions of N-Phenoxyacetamides and Methyleneoxetanones [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3272-3278.
[8]	Yuhe Qiu, Kanghui Lu, Bangchi Wei, Zhenkai Qian, Zhengjie He. P^III-Mediated Intramolecular Cyclopropanation and Synthesis of Cyclopropa[c]coumarins [J]. Chinese Journal of Organic Chemistry, 2021, 41(10): 4066-4074.
[9]	Lu Shengle, Tu Xianxia, Liu Weishun, Shen Liting, Mao Shanjian, Deng Guisheng. Transition Metal-Free-Catalyzed Regioselective Reversal in the Cyclization of 2-Diazo-3,5-dioxo-6-ynoates/ynones/ynamide: Synthesis of Diazo γ-Pyrones and Diazo 3(2H)-Furanones [J]. Chin. J. Org. Chem., 2018, 38(7): 1663-1672.
[10]	Zhu Xinju, Niu Junlong, Zhao Xuemei, Hao Xinqi, Song Maoping. Synthesis of Chiral Bis(imidazoline) Ligands with Biphenyl Backbone and Their Application in the Asymmetric Cyclopropanation Reaction [J]. Chin. J. Org. Chem., 2018, 38(1): 118-123.
[11]	Xu Nanhui, Chen Heru. An Efficient Total Synthesis of Ethyl 7-(Hydroxyimino)cyclopropa-[b]chromen-1a-carboxylate and Their Derivatives [J]. Chin. J. Org. Chem., 2015, 35(5): 1033-1039.
[12]	Cai Shaojun, Xiao Longqiang, Liao Liqiong, Liu Lijian. Catalyst-Free Cyclopropanation of Alkenes with Diazocompounds under Microwave Irradiation [J]. Chin. J. Org. Chem., 2013, 33(12): 2602-2606.
[13]	HE Shi-Hua, WANG Chun-Ting. A Vinyl Epoxide Based Approach to 6β,7β-Methylene in Androstanes [J]. Chin. J. Org. Chem., 2011, 31(03): 379-382.
[14]	Han, Xun^a; Ye, Longwu^b ; Sun, Xiuli^*,b. Cyclization Reactions for the Stereoselective Synthesis of Small Ring Compounds via Selenonium and Telluronium Ylides [J]. Chin. J. Org. Chem., 2009, 29(03): 309-320.
[15]	GAO Jin-Shan, BIAN Qing-Hua, GUO Hong-Chao, WANG Min*. New Advances of Asymmetric Cyclopropanation Reactions Using Chiral Metal Catalysts [J]. Chin. J. Org. Chem., 2007, 27(04): 438-448.