Citation: Wen-Rui Li, Ru-Bing Wang, Huiqiang Wang, Jin-Yao Yong, Yu-Huan Li, Shi-Shan Yu, Shuang-Gang Ma. Ring-reorganization strategy for asymmetric synthesis of sesquiterpenoid illihenin A and its antiviral activity evaluation[J]. Chinese Chemical Letters, ;2025, 36(11): 110945. doi: 10.1016/j.cclet.2025.110945 shu

Ring-reorganization strategy for asymmetric synthesis of sesquiterpenoid illihenin A and its antiviral activity evaluation

Wen-Rui Li ^{a, 1} ,
Ru-Bing Wang ^{a, 1} ,
Huiqiang Wang ^{b, 1} ,
Jin-Yao Yong ^a ,
Yu-Huan Li ^b ,
Shi-Shan Yu ^{a, *,} ,
Shuang-Gang Ma ^{a, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

yushishan@imm.ac.cn

mashuanggang@imm.ac.cn

Received Date: 28 October 2024
Revised Date: 1 February 2025
Accepted Date: 11 February 2025
Available Online: 13 February 2025

Figures(8)

Herein, we report the first asymmetric synthesis of illihenin A, an antiviral sesquiterpenoid bearing a cage-like tricyclo[6.2.2.0^1,5]dodecane skeleton. Starting from an abundant feedstock (-)-α-cedrene, this 19-step synthesis approach features a novel ring-reorganization strategy that includes early stage C7-hydroxylation of the cedrane skeleton and a later-stage ring disassembly-reassembly procedure, affording the desired product with high synthetic efficiency and minimal chiral manipulation. The key transformations include the following: (ⅰ) a hydroxy group-directed SmI₂-mediated reductive coupling to construct the congested tertiary 7-OH cedrane, (ⅱ) a β-fragmentation triggered by an alkoxy radical to release a spiro[4.5]decane, and (ⅲ) an intramolecular Aldol reaction, concomitant with α-epimerization, to furnish the tricyclic framework. In addition, preliminary investigation of antiviral activity against CVB3 revealed that illihenin A can significantly inhibit ROS production and apoptosis.
- Sesquiterpenoid,
- Illihenin A,
- Ring-reorganization,
- Asymmetric synthesis,
- Antiviral activity
1. [1]
  B.M. Fraga, Nat. Prod. Rep. 29 (2012) 1334. doi: 10.1039/c2np20074k
2. [2]
  T. Abu-Izneid, A. Rauf, M.A. Shariati, et al., Pharmacol. Res. 161 (2020) 105165. doi: 10.1016/j.phrs.2020.105165
3. [3]
  D. Chen, J. Li, X. Xu, et al., Chin. Chem. Lett. 35 (2024) 109451. doi: 10.1016/j.cclet.2023.109451
4. [4]
  J. Li, Z. Cui, Y. Li, et al., Chin. Chem. Lett. 35 (2022) 4257–4260.
5. [5]
  T.J. Maimone, P.S. Baran, NatChemBio 3 (2007) 396–407. doi: 10.1038/nchembio.2007.1
6. [6]
  A. Kanwal, M. Bilal, N. Rasool, et al., Pharmaceuticals 15 (2022) 1392. doi: 10.3390/ph15111392
7. [7]
  X. Cheng, G.C. Micalizio, J. Am. Chem. Soc. 138 (2016) 1150–1153. doi: 10.1021/jacs.5b12694
8. [8]
  Y. Zhu, J. Zheng, P.A. Evans, J. Am. Chem. Soc. 145 (2023) 3833–3838. doi: 10.1021/jacs.2c10923
9. [9]
  C. Etling, G. Tedesco, A. Di Marco, et al., J. Am. Chem. Soc. 145 (2023) 7021–7029. doi: 10.1021/jacs.3c01262
10. [10]
  Z.G. Brill, M.L. Condakes, C.P. Ting, et al., Chem. Rev. 117 (2017) 11753–11795. doi: 10.1021/acs.chemrev.6b00834
11. [11]
  J. Kühlborn, J. Groß, T. Opatz, Nat. Prod. Rep. 37 (2020) 380–424. doi: 10.1039/c9np00040b
12. [12]
  R.F. Lusi, M.A. Perea, R. Sarpong, Acc. Chem. Res. 55 (2022) 746–758. doi: 10.1021/acs.accounts.1c00783
13. [13]
  C.S. Harmange Magnani, D.Q. Thach, K.T. Haelsig, et al., Acc. Chem. Res. 53 (2020) 949–961. doi: 10.1021/acs.accounts.0c00055
14. [14]
  K. Hung, M.L. Condakes, T. Morikawa, et al., J. Am. Chem. Soc. 138 (2016) 16616–16619. doi: 10.1021/jacs.6b11739
15. [15]
  M.L. Condakes, K. Hung, S.J. Harwood, et al., J. Am. Chem. Soc. 139 (2017) 17783–17786. doi: 10.1021/jacs.7b11493
16. [16]
  K. Hung, M.L. Condakes, L.F.T. Novaes, et al., J. Am. Chem. Soc. 141 (2019) 3083–3099. doi: 10.1021/jacs.8b12247
17. [17]
  J.-Y. Yong, W.-R. Li, X. Wang, et al., J. Org. Chem. 86 (2021) 2017–2022. doi: 10.1021/acs.joc.0c02727
18. [18]
  D.J. Edmonds, D. Johnston, D.J. Procter, Chem. Rev. 104 (2004) 3371–3404. doi: 10.1021/cr030017a
19. [19]
  K.C. Nicolaou, S.P. Ellery, J.S. Chen, Angew. Chem. Int. Ed. 48 (2009) 7140–7165. doi: 10.1002/anie.200902151
20. [20]
  M. Szostak, N.J. Fazakerley, D. Parmar, et al., Chem. Rev. 114 (2014) 5959–6039. doi: 10.1021/cr400685r
21. [21]
  Y. Gao, D. Ma, Nat. Synth. 1 (2022) 275–288. doi: 10.1038/s44160-022-00046-z
22. [22]
  G.A. Molander, J.A. McKie, J. Org. Chem. 60 (1995) 872–882. doi: 10.1021/jo00109a018
23. [23]
  M. Kawatsura, F. Matsuda, H. Shirahama, J. Org. Chem. 59 (1994) 6900–6901. doi: 10.1021/jo00102a010
24. [24]
  F. Matsuda, J. Syn. Org. Chem. Jpn. 53 (1995) 987–998. doi: 10.5059/yukigoseikyokaishi.53.987
25. [25]
  F. Matsuda, M. Kawatsura, K. Hosaka, et al., Chem. Eur. J. 5 (1999) 3252–3259. doi: 10.1002/(SICI)1521-3765(19991105)5:11<3252::AID-CHEM3252>3.0.CO;2-D
26. [26]
  T. Kan, S. Nara, T. Ozawa, et al., Angew. Chem. Int. Ed. 39 (2000) 355–357. doi: 10.1002/(SICI)1521-3773(20000117)39:2<355::AID-ANIE355>3.0.CO;2-U
27. [27]
  T. Kan, S. Hosokawa, S. Nara, et al., J. Org. Chem. 69 (2004) 8956–8958. doi: 10.1021/jo049203m
28. [28]
  T.K. Hutton, K.W. Muir, D.J. Procter, Org. Lett. 5 (2003) 4811–4814. doi: 10.1021/ol0358399
29. [29]
  A.L.J. Beckwith, Tetrahedron 37 (1981) 3073–3100. doi: 10.1016/S0040-4020(01)98839-8
30. [30]
  E.J. Corey, C.J. Helal, Angew. Chem. Int. Ed. 37 (1998) 1986–2012. doi: 10.1002/(SICI)1521-3773(19980817)37:15<1986::AID-ANIE1986>3.0.CO;2-Z
31. [31]
  S.W. McCombie, W.B. Motherwell, M.J. Tozer, The Barton-McCombie reaction, in: S. E. Denmark, Organic Reactions, John Wiley & Sons, 2012, pp. 161–432.
32. [32]
  D.H.R. Barton, M. Bolton, P.D. Magnus, et al., J. Chem. Soc., Perkin Trans. 1 (1973) 1574–1579.
33. [33]
  J. Chi, S. Yu, C. Liu, et al., Biochem. Biophys. Res. Commun. 503 (2018) 1641–1644. doi: 10.1016/j.bbrc.2018.07.093
34. [34]
  B. Han, T. Wang, Z. Xue, et al., Int. J. Nanomed. 16 (2021) 6035–6048. doi: 10.2147/ijn.s327094
35. [35]
  W. Li, M. Chen, L. Xu, et al., RSC Adv. 9 (2019) 1222–1229. doi: 10.1039/c8ra08662a
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2. [2]
  Min Liu , Di Wang , Zenghui Ye , Donghao Jiang , Bencan Tang , Yanqi Wu , Fengzhi Zhang . Highly stereo- and enantio-selective synthesis of spiro cyclopropyl oxindoles via organic catalyst-mediated cyclopropanation. Chinese Chemical Letters, 2025, 36(10): 110923-. doi: 10.1016/j.cclet.2025.110923
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4. [4]
  Qian Wang , Yeping Bian , Gagan Dhawan , Wei Zhang , Alexander E. Sorochinsky , Ata Makarem , Vadim A. Soloshonok , Jianlin Han . FDA approved fluorine-containing drugs in 2023. Chinese Chemical Letters, 2024, 35(11): 109780-. doi: 10.1016/j.cclet.2024.109780
5. [5]
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6. [6]
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7. [7]
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8. [8]
  Deli Chen , Jiawen Li , Xudong Xu , Zhaocui Sun , Yun Yang , Minghui Xu , Hanqiao Liang , Junshan Yang , Hui Meng , Guoxu Ma , Jianhe Wei . Plant-microbial interactions inspired the discovery of novel sesquiterpenoid dimeric skeletons of hidden natural products from Hibiscus tiliaceus. Chinese Chemical Letters, 2024, 35(10): 109451-. doi: 10.1016/j.cclet.2023.109451
9. [9]
  Juan He , Jiao-Xian Du , Meng Wang , Xiao-Dong Luo , Tao Feng . Irpexlactones A and B, a pair of ring-rearranged tremulane sesquiterpenoids from the basidiomycete Irpex lacteus and their anti-inflammatory activity. Chinese Chemical Letters, 2025, 36(10): 110769-. doi: 10.1016/j.cclet.2024.110769
10. [10]
  Xiang Huang , Dongzhen Xu , Yang Liu , Xia Huang , Yangfan Wu , Dongmei Fang , Bing Xia , Wei Jiao , Jian Liao , Min Wang . Asymmetric synthesis of difluorinated α-quaternary amino acids (DFAAs) via Cu-catalyzed difluorobenzylation of aldimine esters. Chinese Chemical Letters, 2024, 35(12): 109665-. doi: 10.1016/j.cclet.2024.109665
11. [11]
  Guodong Wang , Mengying Jia , Haitao Liu , Yong Liu , Zhiguo Zhang , Xianxiu Xu . Expeditious synthesis and applications of isoquinoline ring-modified Quinap derivatives. Chinese Chemical Letters, 2025, 36(8): 110705-. doi: 10.1016/j.cclet.2024.110705
12. [12]
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13. [13]
  Guoping Yang , Zhoufu Lin , Xize Zhang , Jiawei Cao , Xuejiao Chen , Yufeng Liu , Xiaoling Lin , Ke Li . Assembly of Y(Ⅲ)-containing antimonotungstates induced by malic acid with catalytic activity for the synthesis of imidazoles. Chinese Chemical Letters, 2024, 35(12): 110274-. doi: 10.1016/j.cclet.2024.110274
14. [14]
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15. [15]
  Yuhan Zhang , Xiao-Lin Zhang , Han Ding , Yuan Xu , Xue-Wei Liu . Catalytic ring-strain release toward a facial and efficient synthesis of versatile C-glycosides. Chinese Chemical Letters, 2025, 36(7): 110560-. doi: 10.1016/j.cclet.2024.110560
16. [16]
  Maitri Bhattacharjee , Rekha Boruah Smriti , R. N. Dutta Purkayastha , Waldemar Maniukiewicz , Shubhamoy Chowdhury , Debasish Maiti , Tamanna Akhtar . Synthesis, structural characterization, bio-activity, and density functional theory calculation on Cu(Ⅱ) complexes with hydrazone-based Schiff base ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1409-1422. doi: 10.11862/CJIC.20240007
17. [17]
  Xiaomeng Hu , Jie Yu , Lijie Sun , Linfeng Zhang , Wei Zhou , Dongpeng Yan , Xinrui Wang . Synthesis of an AVB@ZnTi-LDH composite with synergistically enhance UV blocking activity and high stability for potential application in sunscreen formulations. Chinese Chemical Letters, 2024, 35(11): 109466-. doi: 10.1016/j.cclet.2023.109466
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19. [19]
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