Isolation, total synthesis, and biological evaluation of dearomatized isoprenylated acylphloroglucinols from Hypericum przewalskii

doi:10.1007/s13659-026-00626-y

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (4): 47-47.DOI: 10.1007/s13659-026-00626-y

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Isolation, total synthesis, and biological evaluation of dearomatized isoprenylated acylphloroglucinols from Hypericum przewalskii

Yong Li¹, Fei-Fei Xiong^2,3, Xiao-Yang Sun^2,3, Xing-Ren Li², Dao-Feng Chen^1,4, Gang Xu^1,2, Yin Nian², Li-Dong Shao¹

1. Yunnan Key Laboratory of Southern Medicinal Utilization, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China;
2. Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
3. University of Chinese Academy of Sciences, Beijing 100049, China;
4. School of Pharmacy, Institutes of Integrative Medicine, Fudan University, Shanghai 201203, China

Received:2025-12-15 Accepted:2026-03-04 Online:2026-08-29 Published:2026-08-22
Contact: Dao-Feng Chen,E-mail:dfchen@shmu.edu.cn;Gang Xu,E-mail:xugang008@mail.kib.ac.cn;Yin Nian,E-mail:nianyin@mail.kib.ac.cn;Li-Dong Shao,E-mail:shaolidong@ynucm.edu.cn
Supported by:
Yunnan Key Laboratory Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, APR202301, Gang Xu, Yunnan Revitalization Talent Support Program Innovation Team Project, 202305AS350014, Gang Xu.

Isolation, total synthesis, and biological evaluation of dearomatized isoprenylated acylphloroglucinols from Hypericum przewalskii

Yong Li¹, Fei-Fei Xiong^2,3, Xiao-Yang Sun^2,3, Xing-Ren Li², Dao-Feng Chen^1,4, Gang Xu^1,2, Yin Nian², Li-Dong Shao¹

1. Yunnan Key Laboratory of Southern Medicinal Utilization, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China;
2. Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
3. University of Chinese Academy of Sciences, Beijing 100049, China;
4. School of Pharmacy, Institutes of Integrative Medicine, Fudan University, Shanghai 201203, China

通讯作者: Dao-Feng Chen,E-mail:dfchen@shmu.edu.cn;Gang Xu,E-mail:xugang008@mail.kib.ac.cn;Yin Nian,E-mail:nianyin@mail.kib.ac.cn;Li-Dong Shao,E-mail:shaolidong@ynucm.edu.cn
基金资助:
Yunnan Key Laboratory Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, APR202301, Gang Xu, Yunnan Revitalization Talent Support Program Innovation Team Project, 202305AS350014, Gang Xu.

Abstract

Abstract: New dearomatized isoprenylated acylphloroglucinols hyperprzewones A (1) and B (2) were isolated and characterized from the dried aerial parts of Hypericum przewalskii. The structures of these compounds were confirmed by extensive spectroscopic experiments. A facile synthetic route to 1 and 2 was developed via Friedel-Crafts acylation, alkylation, dearomatization, and oxidative [4 + 2] cyclization, giving a 17% overall yield. Moreover, the synthetic derivative 8 exhibited moderate inhibition on T-type calcium channels Ca_v3.2.

Key words: Hypericum przewalskii, Dearomatized isoprenylated acylphloroglucinols (DIAPs), Total synthesis, T-type calcium channels Ca_v3.2

摘要： New dearomatized isoprenylated acylphloroglucinols hyperprzewones A (1) and B (2) were isolated and characterized from the dried aerial parts of Hypericum przewalskii. The structures of these compounds were confirmed by extensive spectroscopic experiments. A facile synthetic route to 1 and 2 was developed via Friedel-Crafts acylation, alkylation, dearomatization, and oxidative [4 + 2] cyclization, giving a 17% overall yield. Moreover, the synthetic derivative 8 exhibited moderate inhibition on T-type calcium channels Ca_v3.2.

关键词: Hypericum przewalskii, Dearomatized isoprenylated acylphloroglucinols (DIAPs), Total synthesis, T-type calcium channels Ca_v3.2

Yong Li, Fei-Fei Xiong, Xiao-Yang Sun, Xing-Ren Li, Dao-Feng Chen, Gang Xu, Yin Nian, Li-Dong Shao. Isolation, total synthesis, and biological evaluation of dearomatized isoprenylated acylphloroglucinols from Hypericum przewalskii[J]. Natural Products and Bioprospecting, 2026, 16(4): 47-47.

References

[1] Singh IP, Bharate SB. Phloroglucinol compounds of natural origin. Nat Prod Rep. 2006;23:558-91.
[2] Ciochina R, Grossman RB. Polycyclic polyprenylated acylphloroglucinols. Chem Rev. 2006;106:3963-86.
[3] Yang XW, Grossman RB, Xu G. Research progress of polycyclic polyprenylated acylphloroglucinols. Chem Rev. 2018;118:3508-58.
[4] Wu SB, Long C, Kennelly EJ. Structural diversity and bioactivities of natural benzophenones. Nat Prod Rep. 2014;31:1158-74.
[5] Guan X, Wang H, Zhang W, Xie Z. Asymmetric total synthesis of (+)-hyperbeanol A. Org Lett. 2025;27:8-13.
[6] Jiang NN, Gar-Lee YG, Li P, Ye YS, Gomes AJ, Hin-Fai KF, et al. Discovery of dearomatized isoprenylated acylphloroglucinols with colon tumor suppressive activities in mice via inhibiting NFκB-FAT1-PDCD4 signaling activation. Eur J Med Chem. 2022;239:114532.
[7] Tao Y, Reisenauer K, Taube JH, Romo D. Total synthesis and anticancer activity of (+)-hypercalin C and congeners. Angew Chem Int Ed Engl. 2019;58:2734-8.
[8] Cheong E, Shin HS. T-Type Ca²⁺ channels in normal and abnormal brain functions. Physiol Rev. 2013;93:961-92.
[9] Kim D, Song I, Keum S, Lee T, Jeong MJ, Kim SS, et al. Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking α_1G T-type Ca²⁺ channels. Neuron. 2001;31:35-45.
[10] Zamponi GW, Striessnig J, Koschak A, Dolphin AC. The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol Rev. 2015;67:821-70.
[11] Tadayonnejad R, Anderson D, Molineux ML, Mehaffey WH, Jayasuriya K, Turner RW. Rebound discharge in deep cerebellar nuclear neurons in vitro. Cerebellum. 2010;9:352-74.
[12] Ye YS, Liu R, Jiang NN, Li SY, Nian Y, Xu G. Caged polycyclic polyprenylated acylphloroglucinols as Cav3.2 low voltage-gated Ca²⁺ channel inhibitors from Hypericum curvisepalum. Chem Commun. 2022;58:13135-8.
[13] Hu YL, Dong D, Zhao JJ, Hu K, Kong LM, Hu YX, et al. 5-Methylated polyprenylated acylphloroglucinol derivatives as low-voltage-gated Ca²⁺ channel inhibitors. Org Chem Front. 2025;12:2375-81.
[14] Ye YS, Wu M, Jiang NN, Lao YZ, Fu WW, Liu X, et al. Dearomatized isoprenylated acylphloroglucinol derivatives with potential antitumor activities from Hypericum henryi. Nat Prod Bioprospect. 2020;10:1-11.
[15] Chauthe SK, Bharate SB, Sabde S, Mitra D, Bhutani KK, Singh IP. Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols. Bioorg Med Chem. 2010;18:2029-36.
[16] Nakagawa G, Wu PC, Bastow KF, Yang SC, Yu SL, Chen HY, Lin JC, Goto M, Morris-Natschke SL, Yang PC, Lee KH. Antitumor agents 283. Further elaboration of desmosdumot in C analogs as potent antitumor agents: activation of spindle assembly checkpoint as possible mode of action. Bioorg Med Chem. 2011;19:1816-22.
[17] Mzozoyana V, Van H, Fanie R. Synthesis of 3-geranyl- and 3-prenyl-2,4,6-trihydroxybenzophenone. Synth Commun. 2017;47:599-603.
[18] George JH, Hesse MD, Baldwin JE, Adlington RM. Biomimetic synthesis of polycyclic polyprenylated acylphloroglucinol natural products isolated from Hypericum papuanum. Org Lett. 2010;12:3532-5.
[19] Kuhnke J, Bohlmann F. Synthesis of naturally occurring phloroglucinol derivatives. Tetrahedron. 1985;26:3955-8.
[20] Yuan ST, Peng YP, Xia D, Jiang J, Li k, Li DS, et al. De novo syntheses of coumaronochromones: application in total synthesis of cristatone II. J Org Chem. 2025;90:7877-87.
[21] Wang X, Lee YR. Efficient synthesis of polycycles bearing prenylated, geranylated, and farnesylated citrans: application to 3'-prenylrubranine and petiolin D regioisomer. Tetrahedron. 2011;67:9179-84.
[22] Elizabeth T, Roland A, Matt T, Kay C, Grisha P, Dharahana R, et al. The synthesis and anticancer effects of a range of natural and unnatural hop β-acids on breast cancer cells. Phytochemistry. 2012;5:144-9.

Isolation, total synthesis, and biological evaluation of dearomatized isoprenylated acylphloroglucinols from Hypericum przewalskii

Isolation, total synthesis, and biological evaluation of dearomatized isoprenylated acylphloroglucinols from Hypericum przewalskii

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