Applications of Palladium-Catalyzed Cascade Reactions in Total Synthesis of Complex Natural Products with Quaternary Carbon Centers

doi:10.6023/cjoc202502022

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (9): 3289-3300.DOI: 10.6023/cjoc202502022 Previous Articles Next Articles

REVIEWS

钯催化串联反应在含季碳中心的复杂天然产物全合成中的应用

赵倩倩^*(), 魏培垚, 刘孙典, 张博鑫, 梁承远^*()

陕西科技大学食品科学与工程学院西安 710021

收稿日期:2025-02-19 修回日期:2025-04-15 发布日期:2025-05-20
基金资助:
国家自然科学基金(32200315); 陕西省科技厅重点研发计划(2024NC-YBXM-256); 陕西省教育厅重点科学研究计划(University Engineering Research Center Projec, No. 24JR039)

Applications of Palladium-Catalyzed Cascade Reactions in Total Synthesis of Complex Natural Products with Quaternary Carbon Centers

Qianqian Zhao^*(), Peiyao Wei, Sundian Liu, Boxin Zhang, Chengyuan Liang^*()

School of Food Science and Engineering, Shaanxi University of Science & Technology, Xi'an 710021

Received:2025-02-19 Revised:2025-04-15 Published:2025-05-20
Contact: *E-mail: zhaoqianqian@sust.edu.cn; chengyuanliang@gmail.com
Supported by:
National Natural Science Foundation of China(32200315); Key R&D Project of Science and Technology Department of Shaanxi Province(2024NC-YBXM-256); Key Scientific Research Program of Shaanxi Provincial Department of Education(University Engineering Research Center Projec, No. 24JR039)

Quaternary carbon centers (including all-carbon quaternary centers and heteroatom-contained quaternary carbon centers) are widely present in the core skeletons of natural products and functional molecules, and their contribution to the complexity of molecular structures is also of great significance. However, due to the complex chemical structures and significant steric hindrance effects of quaternary carbon centers, the synthesis of such structural units is fraught with enormous challenges. Palladium-catalyzed cascade reaction plays an important role in the synthesis of the complex natural products. In particular, it shows significant advantages in construction of quaternary carbon centers. The development of application of palladium-catalyzed cascade reaction in the establishment of complex framework with quaternary carbon centers and further total synthesis of corresponding natural products in the last 10 years is introduced.

Key words: palladium-catalyzed cascade reaction, complex natural product, total synthesis, construction of quaternary carbon center

Cite this article

Qianqian Zhao, Peiyao Wei, Sundian Liu, Boxin Zhang, Chengyuan Liang. Applications of Palladium-Catalyzed Cascade Reactions in Total Synthesis of Complex Natural Products with Quaternary Carbon Centers[J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3289-3300.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 15

Figure 1. Representative molecules of natural products synthesized through palladium-catalyzed cascade reaction

Scheme 1. Total synthesis of hexahydropyrroloindole alkaloids (＋)-esermethole (6a) and (＋)-physostigmine (6b)

Scheme 2. Total synthesis of hexahydropyrroloindole alkaloids 11~13 and 15

Scheme 3. Total synthesis of (-)‑N‑methylwelwitindolinone C isothiocyanate (24)

Scheme 4. Total synthesis of (-)-presilphiperfolan-8-ol (32)

Scheme 5. Establishment of synthetic method towards oxaspirolactone unit and total synthesis of the C(12) oxygenated labdanolic diterpenes α-levantanolide (34a) and α-levantenolide (39)

Scheme 6. Total synthesis of stemona alkaloids 48 and 50

Scheme 7. Total synthesis of cyclopianes diterpenes

Scheme 8. Total synthesis of (＋)-perseanol (72)

Scheme 9. Total synthesis of schizozygane alkaloids

Scheme 10. Total synthesis of galanthamine (94) and lycoramine (95)

Scheme 11. Total synthesis of metaphanine (104) and oxoepistephamiersine (105)

Scheme 12. Total synthesis of (-)-garryine (111)

Scheme 13. Total synthesis of euphorbialoid A (119)

Scheme 14. Total synthesis of garajonone (129)

References 27

[1]	(a) Shao, H.; Zhao, Y.-M. Sci. Sin.: Chim. 2024, 54, 1619. pmid: 12914487
	(b) Sims, H. S.; Dai, M. J. Org. Chem. 2023, 88, 4925. pmid: 12914487
	(c) Peng, J.-B.; Liu, X.-L.; Li, L.; Wu, X.-F. Sci. China: Chem. 2022, 65, 441. pmid: 12914487
	(d) Holman, K. R.; Stanko, A. M.; Reisman, S. E. Chem. Soc. Rev. 2021, 50, 7891. pmid: 12914487
	(e) Ma, K.; Martin, B. S.; Yin, X.; Dai, M. Nat. Prod. Rep. 2019, 36, 174. pmid: 12914487
	(f) Bai, Y.; Davis, D. C.; Dai, M. J. Org. Chem. 2017, 82, 2319. doi: 10.1021/acs.joc.7b00009 pmid: 12914487
	(g) Wu, X.-F.; Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 1. pmid: 12914487
	(h) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945. pmid: 12914487
[2]	Crich, D.; Banerjee, A. Acc. Chem. Res. 2007, 40, 151.
[3]	(a) Kong, W.; Wang, Q.; Zhu, J. J. Am. Chem. Soc. 2015, 137, 16028.
	(b) Pinto, A.; Jia, Y.; Neuville, L.; Zhu, J. Chem.-Eur. J. 2007, 13, 961.
	(c) For alternative cyanoamidation of alkenes, see: Yasui, Y.; Kamisaki, H.; Takemoto, Y. Org. Lett. 2008, 10, 3303.
[4]	(a) Chen, M.; Wang, X.; Yang, P.; Kou, X.; Ren, Z.-H.; Guan, Z.-H. Angew. Chem., Int. Ed. 2020, 59, 12199.
	(b) Matsuura, T.; Overman, L. E.; Poon, D. J. J. Am. Chem. Soc. 1998, 120, 6500.
[5]	(a) Stratmann, K.; Moore, R. E.; Bonjouklian, R.; Deeter, J. B.; Patterson, G. M. L.; Shaffer, S.; Smith, C. D.; Smitka, T. A. J. Am. Chem. Soc. 1994, 116, 9935. pmid: 10217710
	(b) Jimenez, J. I.; Huber, U.; Moore, R. E.; Patterson, G. M. L. J. Nat. Prod. 1999, 62, 569. pmid: 10217710
[6]	Komine, K.; Nomura, Y.; Ishihara, J.; Hatakeyama, S. Org. Lett. 2015, 17, 3918. doi: 10.1021/acs.orglett.5b01952 pmid: 26214342
[7]	(a) Bohlmann, F.; Zdero, C.; Jakupovic, J.; Robinson, H.; King, R. M. Phytochemistry 1981, 20, 2239.
	(b) Coates, R. M.; Ho, Z.; Klobus, M.; Wilson, S. R. J. Am. Chem. Soc. 1996, 118, 9249.
[8]	Hu, P.; Snyder, S. A. ; J. Am. Chem. Soc. 2017, 139, 5007.
[9]	Davis, D. C.; Walker, K. L.; Hu, C.; Zare, R. N.; Waymouth, R. M.; Dai, M. J. Am. Chem. Soc. 2016, 138, 10693.
[10]	Lin, L.-G.; Zhong, Q. X.; Cheng, T. Y.; Tang, C. P.; Ke, C.-Q.; Lin, G.; Ye, Y. J. Nat. Prod. 2006, 69, 1051. pmid: 16872143
[11]	Ma, K.; Yin, X.; Dai, M. Angew. Chem., Int. Ed. 2018, 57, 15209.
[12]	(a) Roncal, T.; Cordobés, S.; Ugalde, U.; He, Y.; Sterner, O. Tetrahedron Lett. 2002, 43, 6799.
	(b) Du, L.; Li, D.; Zhu, T.; Cai, S.; Wang, F.; Xiao, X.; Gu, Q. Tetrahedron 2009, 65, 1033.
[13]	Hu, P.; Chi, H. M.; DeBacker, K. C.; Gong, X.; Keim, J. H.; Hsu, I. T.; Snyder, S. A. Nature 2019, 569, 703.
[14]	González-Coloma, A.; Terrero, D.; Perales, A.; Escoubas, P.; Fraga, B. M. J. Agric. Food Chem. 1996, 44, 296.
[15]	Han, A.; Tao, Y.; Reisman, S. E. Nature 2019, 573, 563.
[16]	(a) Atilaw, Y.; Heydenreich, M.; Ndakala, A.; Akala, H. M.; Kamau, E.; Yenesew, A. Phytochem. Lett. 2014, 10, 28. pmid: 11137346
	(b) Kariba, R. M.; Houghton, P. J.; Yenesew, A. J. Nat. Prod. 2002, 65, 566. pmid: 11137346
	(c) Stephens, P. J.; Pan, J.-J.; Devlin, F. J.; Urbanová, M.; Hájícek, J. J. Org. Chem. 2007, 72, 2508. pmid: 11137346
	(d) Kariba, R. M.; Siboe, G. M.; Dossaji, S. F. J. Ethnopharmacol. 2001, 74, 41. pmid: 11137346
[17]	Zhou, W.; Zhou, T.; Tian, M.; Jiang, Y.; Yang, J.; Lei, S.; Wang, Q.; Zhang, C.; Qiu, H.; He, L.; Wang, Z.; Deng, J.; Zhang, M. J. Am. Chem. Soc. 2021, 143, 19975.
[18]	Marco-Contelles, J.; do Carmo Carreiras, M.; RodrÍguez, C.; Villarroya, M.; GarcÍa, A. G. Chem. Rev. 2006, 106, 116. pmid: 16402773
[19]	Chang, Y.-P.; Ma, X.; Shao, H.; Zhao, Y.-M. Org. Lett. 2021, 23, 9659.
[20]	King, S. M.; Herzon, S. B. In The Alkaloids: Chemistry and Biology, Vol. 73, Ed.: Knölker, H.-J., Academic Press, Burlington, 2014, p. 161.
[21]	Sun, Y.-K.; Qiao, J.-B.; Xin, Y.-M.; Zhou, Q.; Ma, Z.-H.; Shao, H.; Zhao, Y.-M. Angew. Chem., Int. Ed. 2023, 62, e202310917.
[22]	(a) Oneto, J. F. J. Am. Pharm. Assoc., Sci. Ed. 1946, 35, 204.
	(b) Powell, C. E.; Herrmann, R. G.; Chen, K. K. J. Am. Pharm. Assoc., Sci. Ed. 1956, 45, 733.
[23]	Li, C.; Lu, F.; Cai, Y.; Zhang, C.; Shao, Y.; Zhang, Y.; Liu, X.-Y.; Qin, Y. J. Am. Chem. Soc. 2024, 146, 1081.
[24]	Xu, J.; Jin, D.-Q.; Guo, Y.; Xie, C.; Ma, Y.; Yamakuni, T.; Ohizumi, Y. Bioorg. Med. Chem. Lett. 2012, 22, 3612.
[25]	Taguchi, J.; Fukaya, S.; Fujino, H.; Inoue, M. J. Am. Chem. Soc. 2024, 146, 34221.
[26]	(a) Fraga, B. M.; Díaz, C. E.; Bolaños, P.; Bailén, M.; Andrés, M. F.; González-Coloma, A. Phytochemistry 2020, 176, 112398. pmid: 11249093
	(b) Fraga, B. M.; Terrero, D.; Gutiérrez, C.; González-Coloma, A. Phytochemistry 2001, 56, 315. pmid: 11249093
[27]	Qiao, J.-B.; Meng, L.; Pei, J.-Y.; Shao, H.; Zhao, Y.-M. Angew. Chem., Int. Ed. 2024, e202417647.

钯催化串联反应在含季碳中心的复杂天然产物全合成中的应用

Applications of Palladium-Catalyzed Cascade Reactions in Total Synthesis of Complex Natural Products with Quaternary Carbon Centers

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 15

References 27

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Ying Xia, Chenlong Zhu, Bingfeng Sun. Progress in Total Synthesis of Entecavir, an Antiviral Drug for Hepatitis B^★ [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3186-3202.
[2]	Xiaoyu Liu, Tingrui Xu, Yong Qin. Recent Progress in the Total Synthesis of Morphine Alkaloids^★ [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3098-3112.
[3]	Baichuan Mo, Tingting Li, Fang Wang, Xiaojie Li, Darifu Ba. Recent Progress in the Synthesis of Carbazolequinone Natural Products [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2746-2766.
[4]	Yiming Ding, Tingrong Zhang, Jingwei Zhang, Jun Deng. Progress in the Total Synthesis of Cephalotane Diterpenoid Natural Products [J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2048-2073.
[5]	Weigang He, Yadong Liu, Yingkai Deng, Xianyu Sun. Recent Progress in the Synthesis of the Malagasy Alkaloids [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1153-1165.
[6]	Shoule Han, Mingliang Lou, Xiaolei Liu, Gen Li, Xin Wang, Qingcui Wu, Xiangbing Qi. Divergent Hydrogenation of Indoles and Its Applications in Total Syntheses of (±)-α- and γ-Lycoranes [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 913-924.
[7]	Jie Chen, Jun Li, Xianwen Long, Haixiang Shen, Jun Deng. Recent Advances of Wagner-Meerwein Rearrangement in Natural Product Synthesis [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 896-912.
[8]	Long Meng, Jin-Bao Qiao, Yu-Ming Zhao. Progress on the Total Synthesis of Ryania Diterpenoids [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 804-813.
[9]	Xiaofeng Zhang, Aggeliki Roumana, Haikang Mao, Jing Xu. Synthesis of the AB Ring System of Daphniphyllum Alkaloid Daphniglaucin C [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 925-932.
[10]	Haikang Mao, Jing Xu. Recent Progress in the Total Synthesis of Daphniphyllum Alkaloids [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 866-880.
[11]	Jiuzhou Yi, Liang Huo, Jinyan Chen, Meng Liu, Huilin Li, Xuegong She. Protecting Group Effects on the Total Syntheses of Several Classes of Natural Products [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 1030-1039.
[12]	Yunbo Yang, Hanfeng Ding. Advances in the Total Syntheses of Tetraquinane and Tetraquinane-Type Terpenes [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 725-747.
[13]	Qingxing Yang, Xuan Liu, Shuo Ma, Xinxin Li, Dongxu Ma, Tao Xu. Total Syntheses of Marine-Derived Polyhalogenated Natural Products [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 764-803.
[14]	Chuang Li, Cheng Zhang, Xiaoyu Liu, Yong Qin. Recent Progress in the Total Synthesis of Diterpenoid Alkaloids [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 881-895.
[15]	Xuge Si, Quan Cai. Asymmetric Total Synthesis and Structural Revision of Antiangiogenic Natural Product Penduliflaworosin [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 959-968.