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

doi:10.6023/cjoc202507021

摘要/Abstract

吲哚生物碱分布广泛、结构复杂, 并且具有丰富的药理活性, 是目前天然产物全合成领域的研究热点. 生物碱arboridinine和arborisidine是从马来西亚的蕊木属植物中分离得到的, 这两个生物碱特殊而高度复杂的笼状结构使其全合成研究极具挑战性, 因此得到了广泛关注. 本文总结了arboridinine和arborisidine的全合成研究进展, 以期为相关天然产物的全合成提供参考.

关键词: 生物碱, 全合成, arboridinine, arborisidine

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

引用此文

何卫刚, 段明月, 闫帅, 叶伟杰, 徐雪园, 孙先宇. 蕊木属生物碱arboridinine和arborisidine的全合成研究进展[J]. 有机化学, 2026, 46(2): 443-454.

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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图/表 13

图1. Arboridinine和arborisidine以及相关的吲哚生物碱

Figure 1. Arboridinine, arborisidine and related indole alkaloids

图式1. Snyder课题组的arboridinine全合成路线

Scheme 1. Snyder’s total synthesis route of arboridinine

图式2. Snyder课题组的arborisidine全合成路线

Scheme 2. Snyder’s total synthesis route of arborisidine

图式3. 翟宏斌、李云课题组的arboridinine全合成路线

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

图式4. 祝介平课题组的arborisidine全合成路线

Scheme 4. Zhu’s total synthesis route of arborisidine

图式5. 焦雷课题组的arborisidine全合成路线

Scheme 5. Jiao’s total synthesis route of arborisidine

图式6. 马志强课题组发散式合成arboridinine和arborisidine的四环核心骨架

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

图式7. 马志强课题组对arboridinine和arborisidine的全合成路线

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

图式8. 马志强课题组对arboridinine的形式全合成路线

Scheme 8. Ma’s formal synthesis route of arboridinine

图式9. 厍学功、曹小平课题组对arborisidine的形式全合成路线

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

图式10. 秦勇、宋颢课题组对arborisidine四环骨架的全合成路线

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

图式11. Arborisidine四环骨架的构建策略

Scheme 11. Construction strategy of the tetracyclic skeleton of arborisidine

图2. Arboridinine和arborisidine的合成策略总结

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

参考文献 33

[1]	Norwood IV V. M.; Huigens III R. W. ChemBioChem 2019, 20, 2273.
[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.
[4]	a) Wang N.; Jiang X. Chem. Rec. 2021, 21, 295.
	(b) Wang N.; Xiao X.; Liu C.-X.; Yao H.; Huang N.; Zou K. Adv. Synth. Catal. 2022, 364, 2479.
[5]	Wong S. P.; Gan C. Y.; Lim K. H.; Ting K. N.; Low Y. Y.; Kam T. S. Org. Lett. 2015, 17, 3628.
[6]	Wong S. P.; Chong K. W.; Lim K. H.; Lim S. H.; Low Y. Y.; Kam T. S. Org. Lett. 2016, 18, 1618.
[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.)
[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.
[9]	Qin B.; Wang Y.; Wang X.; Jia Y. Org. Chem. Front. 2021, 8, 369.
[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.
[12]	Zhou Z.; Gao A. X.; Snyder S. J. Am. Chem. Soc. 2019, 141, 7715.
[13]	Lee J. Y.; You Y. S.; Kang S. H. J. Am. Chem. Soc. 2011, 133, 1772.
[14]	Smith M. W.; Zhou Z.; Gao A. X.; Shimbayashi T.; Snyder S. A. Org. Lett. 2017, 19, 1004.
[15]	Zhang Z.; Xie S.; Cheng B.; Zhai H.; Li Y. J. Am. Chem. Soc. 2019, 141, 7147.
[16]	Xu K.; Wang Z.-Q.; Zhang J.-J.; Yu L.-T.; Tan J.-J. Org. Lett. 2015, 17, 4476.
[17]	Andres R.; Wang Q.; Zhu J. J. Am. Chem. Soc. 2020, 142, 14276.
[18]	Martin C. L.; Overman L. E.; Rohde J. M. J. Am. Chem. Soc. 2010, 132, 4894.
[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.
[20]	Klausen R. S.; Kennedy C. R.; Hyde A. M.; Jacobsen E. N. J. Am. Chem. Soc. 2017, 139, 12299.
[21]	Glinsky-Olivier N.; Yang S.; Retailleau P.; Gandon V.; Guinchard X. Org. Lett. 2019, 21, 9446.
[22]	Wang F. Y.; Jiao L. Angew. Chem. Int. Ed. 2021, 60, 12732.
[23]	Dehli J. R.; Gotor V. Chem. Soc. Rev. 2002, 31, 365.
[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.
[25]	Schreiber S. L. Science 2000, 287, 1964.
[26]	Wu J.; Pang Y.; Jiang H.;Ma. Z. J. Org. Chem. 2022, 87, 8223.
[27]	Hou L.; Yang Y.; Gao X.; Chen W.; She X.; Cao X.-P. Org. Lett. 2024, 26, 3801.
[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).
	( 陈志涛, 肖涛, 宋颢, 秦勇, 有机化学, 2018, 38, 2427.)
[29]	Shen L.; Zhang M.; Wu Y.; Qin Y. Angew. Chem. Int. Ed. 2008, 47, 3618.
[30]	Zhang M.; Huang X.; Shen L.; Qin Y. J. Am. Chem. Soc. 2009, 131, 6013
[31]	a) Xiao T.; Chen Z.-T.; Deng L.-F.; Zhang D.; Liu X.-Y.; Song H.; Qin Y. Chem. Commun. 2017, 53, 12665.
	(b) Chen Z.-T.; Xiao T.; Tang P.; Zhang D.; Qin Y. Tetrahedron 2018, 74, 1129.
[32]	a) Delgado R.; Blakey S. B. Eur. J. Org. Chem. 2009, 1506.
	(b) Andreansky E. S.; Blakey S. B. Org. Lett. 2016, 18, 6492.
[33]	Robert E. G. L.; Pirenne V.; Wodrich M. D.; Waser J. Angew. Chem. Int. Ed. 2023, 62, e202302420.