Progress in the Total Synthesis of the Kopsia Alkaloids Arboridinine and Arborisidine

doi:10.6023/cjoc202507021

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (2): 443-454.DOI: 10.6023/cjoc202507021 Previous Articles Next Articles

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蕊木属生物碱arboridinine和arborisidine的全合成研究进展

何卫刚^a^,^b^,^*(), 段明月^a, 闫帅^a, 叶伟杰^a, 徐雪园^a, 孙先宇^a^,^*()

^a 苏州工学院生物与食品工程学院江苏常熟 215500
^b 中国药科大学药学院南京 210009

收稿日期:2025-07-15 修回日期:2025-09-04 发布日期:2025-10-14
通讯作者: 何卫刚, 孙先宇
基金资助:
国家自然科学基金(22401019)

Progress in the Total Synthesis of the Kopsia Alkaloids Arboridinine and Arborisidine

Weigang He^a^,^b^,^*(), Mingyue Duan^a, Shuai Yan^a, Weijie Ye^a, Xueyuan Xu^a, Xianyu Sun^a^,^*()

^a School of Biology and Food Engineering, Suzhou University of Technology, Changshu, Jiangsu 215500
^b School of Pharmacy, China Pharmaceutical University, Nanjing 210009

Received:2025-07-15 Revised:2025-09-04 Published:2025-10-14
Contact: Weigang He, Xianyu Sun
Supported by:
National Natural Science Foundation of China(22401019)

Indole alkaloids are widely distributed in nature and have rich pharmacological activities, so many indole alkaloids have emerged as hot targets for the total synthesis of natural products. The alkaloids arboridinine and arborisidine were isolated from a plant of the Kopsia genus found in Malaysia by Kam and co-workers in 2015 and 2016, respectively. These two pentacyclic monoterpenoid indole alkaloids have unique caged skeleton with multiple chiral centers. The highly complex cage structure of these alkaloids has brought great challenges to their total synthesis research. In addition, arborisidine combined with pimelautide exhibits clear anti-gastric cancer activity. The complex and attractive chemical structure and potential pharmacological activity, together with an extremely low natural abundance make their total synthesis extremely attractive. Soon after the isolation, their total synthesis has received extensive and sustained attention. Up to now, the total synthesis of arboridinine has be achieved by the Snyder, Ma, Zhai and Li groups, and the total synthesis of arborisidine by the Snyder, Ma, Zhu, Jiao, She and Gao groups. This review summarizes the research progress of total synthesis of arboridinine and arborisidine, in order to provide reference for the total synthesis of the related natural products.

Key words: alkaloids, total synthesis, arboridinine, arborisidine

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Weigang He, Mingyue Duan, Shuai Yan, Weijie Ye, Xueyuan Xu, Xianyu Sun. Progress in the Total Synthesis of the Kopsia Alkaloids Arboridinine and Arborisidine[J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 443-454.

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Fig. & Tab. 13

Figure 1. Arboridinine, arborisidine and related indole alkaloids

Scheme 1. Snyder’s total synthesis route of arboridinine

Scheme 2. Snyder’s total synthesis route of arborisidine

Scheme 3. Zhai and Li’s total synthesis route of arboridinine

Scheme 4. Zhu’s total synthesis route of arborisidine

Scheme 5. Jiao’s total synthesis route of arborisidine

Scheme 6. Ma’s divergent synthesis of the tetracyclic cores of arboridinine and arborisidine

Scheme 7. Ma’s total synthesis route of arboridinine and arborisidine

Scheme 8. Ma’s formal synthesis route of arboridinine

Scheme 9. She and Cao’s formal synthesis route of arborisidine

Scheme 10. Qin and Song’s synthesis route of the tetracyclic skeleton of arborisidine

Scheme 11. Construction strategy of the tetracyclic skeleton of arborisidine

Figure 2. Summary of the synthesis strategies of arboridinine and arborisidine

References 33

[1]	Norwood IV V. M.; Huigens III R. W. ChemBioChem 2019, 20, 2273. doi: 10.1002/cbic.v20.18
[2]	(a) Tu Y. Q. Sci. Focus 2012, 7, 59 (in Chinese).
	(涂永强, 科学观察, 2012, 7, 59.)
	(b) Guo R. X.; Li L. G.; Wang Y. F.; Huo C. H.; Fu Y.; Wang L.; Shi Q. W. Chin. Tradit. Herb. Drugs 2015, 46, 2019 (in Chinese).
	(郭瑞霞, 李力更, 王于方, 霍长虹, 付炎, 王磊, 史清文, 中草药, 2015, 46, 2019.)
[3]	Subramaniam G.; Hiraku O.; Hayashi M.; Koyano T.; Komiyama K.; Kam T. S. J. Nat. Prod. 2007, 70, 1783. pmid: 17939738
[4]	(a) Wang N.; Jiang X. Chem. Rec. 2021, 21, 295. doi: 10.1002/tcr.v21.2
	(b) Wang N.; Xiao X.; Liu C.-X.; Yao H.; Huang N.; Zou K. Adv. Synth. Catal. 2022, 364, 2479. doi: 10.1002/adsc.v364.15
[5]	Wong S. P.; Gan C. Y.; Lim K. H.; Ting K. N.; Low Y. Y.; Kam T. S. Org. Lett. 2015, 17, 3628. doi: 10.1021/acs.orglett.5b01757
[6]	Wong S. P.; Chong K. W.; Lim K. H.; Lim S. H.; Low Y. Y.; Kam T. S. Org. Lett. 2016, 18, 1618. doi: 10.1021/acs.orglett.6b00478
[7]	Liu X.; Xiao T.; Qin Y. Prog. Chem. 2018, 30, 578 (in Chinese).
	(刘小宇, 肖涛, 秦勇, 化学进展, 2018, 30, 578.) doi: 10.7536/PC171131
[8]	Yang Z.; Tan Q.; Jiang Y.; Yang J.; Su X.; Qiao Z.; Zhou W.; He L.; Qiu H.; Zhang M. Angew. Chem. Int. Ed. 2021, 60, 13105. doi: 10.1002/anie.v60.23
[9]	Qin B.; Wang Y.; Wang X.; Jia Y. Org. Chem. Front. 2021, 8, 369. doi: 10.1039/D0QO01165G
[10]	Zhuang H.; Wei S.CN 106540237, 2016.
[11]	Gan P.; Pitzen J.; Qu P.; Snyder S. A. J. Am. Chem. Soc. 2018, 140, 919. doi: 10.1021/jacs.7b07724
[12]	Zhou Z.; Gao A. X.; Snyder S. J. Am. Chem. Soc. 2019, 141, 7715. doi: 10.1021/jacs.9b03248
[13]	Lee J. Y.; You Y. S.; Kang S. H. J. Am. Chem. Soc. 2011, 133, 1772. doi: 10.1021/ja1103102
[14]	Smith M. W.; Zhou Z.; Gao A. X.; Shimbayashi T.; Snyder S. A. Org. Lett. 2017, 19, 1004. doi: 10.1021/acs.orglett.6b03839
[15]	Zhang Z.; Xie S.; Cheng B.; Zhai H.; Li Y. J. Am. Chem. Soc. 2019, 141, 7147. doi: 10.1021/jacs.9b02362 pmid: 30955337
[16]	Xu K.; Wang Z.-Q.; Zhang J.-J.; Yu L.-T.; Tan J.-J. Org. Lett. 2015, 17, 4476. doi: 10.1021/acs.orglett.5b02142
[17]	Andres R.; Wang Q.; Zhu J. J. Am. Chem. Soc. 2020, 142, 14276. doi: 10.1021/jacs.0c05804 pmid: 32692169
[18]	Martin C. L.; Overman L. E.; Rohde J. M. J. Am. Chem. Soc. 2010, 132, 4894. doi: 10.1021/ja100178u
[19]	Wang S.-G.; Xia Z.-L.; Xu R.-Q.; Liu X.-J.; Zheng C.; You S.-L. Angew. Chem. Int. Ed. 2017, 56, 7440. doi: 10.1002/anie.v56.26
[20]	Klausen R. S.; Kennedy C. R.; Hyde A. M.; Jacobsen E. N. J. Am. Chem. Soc. 2017, 139, 12299. doi: 10.1021/jacs.7b06811
[21]	Glinsky-Olivier N.; Yang S.; Retailleau P.; Gandon V.; Guinchard X. Org. Lett. 2019, 21, 9446. doi: 10.1021/acs.orglett.9b03656 pmid: 31725302
[22]	Wang F. Y.; Jiao L. Angew. Chem. Int. Ed. 2021, 60, 12732. doi: 10.1002/anie.v60.23
[23]	Dehli J. R.; Gotor V. Chem. Soc. Rev. 2002, 31, 365. pmid: 12491751
[24]	Wang C.; Pang Y.; Wu Y.; Zhang N.; Yang R.; Li Y.; Chen P.; Jiang H.; Xu X. T.; Kam T. S.; Fan T.; Ma Z. Angew. Chem. Int. Ed. 2021, 60, 26978. doi: 10.1002/anie.v60.52
[25]	Schreiber S. L. Science 2000, 287, 1964. doi: 10.1126/science.287.5460.1964 pmid: 10720315
[26]	Wu J.; Pang Y.; Jiang H.;Ma. Z. J. Org. Chem. 2022, 87, 8223. doi: 10.1021/acs.joc.2c00602
[27]	Hou L.; Yang Y.; Gao X.; Chen W.; She X.; Cao X.-P. Org. Lett. 2024, 26, 3801. doi: 10.1021/acs.orglett.4c00928
[28]	(a) Chen Z. T. Ph.D. Dissertation, Chongqing University, Chongqing, 2019 (in Chinese).
	(陈志涛, 博士论文, 重庆大学, 重庆, 2019.)
	(b) Chen Z.; Xiao T.; Song H.; Qin Y. Chin. J. Org. Chem. 2018, 38, 2427 (in Chinese). doi: 10.6023/cjoc201805025
	(陈志涛, 肖涛, 宋颢, 秦勇, 有机化学, 2018, 38, 2427.) doi: 10.6023/cjoc201805025
[29]	Shen L.; Zhang M.; Wu Y.; Qin Y. Angew. Chem. Int. Ed. 2008, 47, 3618. doi: 10.1002/anie.v47:19
[30]	Zhang M.; Huang X.; Shen L.; Qin Y. J. Am. Chem. Soc. 2009, 131, 6013 doi: 10.1021/ja901219v pmid: 19326910
[31]	(a) Xiao T.; Chen Z.-T.; Deng L.-F.; Zhang D.; Liu X.-Y.; Song H.; Qin Y. Chem. Commun. 2017, 53, 12665. doi: 10.1039/C7CC08153G
	(b) Chen Z.-T.; Xiao T.; Tang P.; Zhang D.; Qin Y. Tetrahedron 2018, 74, 1129. doi: 10.1016/j.tet.2018.01.034
[32]	(a) Delgado R.; Blakey S. B. Eur. J. Org. Chem. 2009, 1506. pmid: 27978638
	(b) Andreansky E. S.; Blakey S. B. Org. Lett. 2016, 18, 6492. pmid: 27978638
[33]	Robert E. G. L.; Pirenne V.; Wodrich M. D.; Waser J. Angew. Chem. Int. Ed. 2023, 62, e202302420.

蕊木属生物碱arboridinine和arborisidine的全合成研究进展

Progress in the Total Synthesis of the Kopsia Alkaloids Arboridinine and Arborisidine

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