Prenylated acylphloroglucinols from the fruits of Hypericum patulum

doi:10.1007/s13659-026-00629-9

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (4): 57-57.DOI: 10.1007/s13659-026-00629-9

• ORIGINAL ARTICLES • Previous Articles Next Articles

Prenylated acylphloroglucinols from the fruits of Hypericum patulum

Yu-Feng Qiu¹, Yi Zhou¹, Cheng Chen³, Juan Huang², Xing-Wei Yang¹

1. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 518107, People's Republic of China;
2. State Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China;
3. Department of Pharmacology, Shanghai Medicilon Inc., Shanghai, China

Received:2026-01-06 Accepted:2026-03-12 Online:2026-08-29 Published:2026-08-22
Contact: Juan Huang,E-mail:huang_juan_2020@163.com;Xing-Wei Yang,E-mail:yang-xingwei@foxmail.com
Supported by:
The authors would like to thank the Natural Sciences Foundation of Guangdong Province (No. 2025A1515010551) and the Shenzhen Medical Research Funds (A2303041). The project was also funded by Shanghai Pujiang Program (No. 2021PJD091) and Shenzhen High-level Hospital Construction Fund (GSP-ZDSYS-009, GSP-QNPY-A2025004).

Prenylated acylphloroglucinols from the fruits of Hypericum patulum

Yu-Feng Qiu¹, Yi Zhou¹, Cheng Chen³, Juan Huang², Xing-Wei Yang¹

1. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 518107, People's Republic of China;
2. State Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China;
3. Department of Pharmacology, Shanghai Medicilon Inc., Shanghai, China

通讯作者: Juan Huang,E-mail:huang_juan_2020@163.com;Xing-Wei Yang,E-mail:yang-xingwei@foxmail.com
基金资助:
The authors would like to thank the Natural Sciences Foundation of Guangdong Province (No. 2025A1515010551) and the Shenzhen Medical Research Funds (A2303041). The project was also funded by Shanghai Pujiang Program (No. 2021PJD091) and Shenzhen High-level Hospital Construction Fund (GSP-ZDSYS-009, GSP-QNPY-A2025004).

Abstract

Abstract: Twenty-eight prenylated acylphloroglucinols, including the new hypulatones C-F (1-4), have been isolated from the fruits of Hypericum patulum and structurally characterized. Compound 1 represents a rare meroterpenoid formed through the addition of a prenylated acylphloroglucinol unit and a sesquiterpenoid moiety. Spirocyclic polycyclic polyprenylated acylphloroglucinol 2 contains six chiral centers, and its relative configuration was established based on ¹H-¹H coupling constants, conformational analysis, and NOE correlations. The cytotoxic activities of all isolates against two human carcinoma cell lines (Huh-7 and Panc-1) were evaluated using the CCK-8 assay. Bioassay results indicated that compounds 6, 8, and 15 exhibited moderate antiproliferative activity.

Key words: Prenylated acylphloroglucinols, Hypericum patulum, Structural determination, Cytotoxicity

摘要： Twenty-eight prenylated acylphloroglucinols, including the new hypulatones C-F (1-4), have been isolated from the fruits of Hypericum patulum and structurally characterized. Compound 1 represents a rare meroterpenoid formed through the addition of a prenylated acylphloroglucinol unit and a sesquiterpenoid moiety. Spirocyclic polycyclic polyprenylated acylphloroglucinol 2 contains six chiral centers, and its relative configuration was established based on ¹H-¹H coupling constants, conformational analysis, and NOE correlations. The cytotoxic activities of all isolates against two human carcinoma cell lines (Huh-7 and Panc-1) were evaluated using the CCK-8 assay. Bioassay results indicated that compounds 6, 8, and 15 exhibited moderate antiproliferative activity.

关键词: Prenylated acylphloroglucinols, Hypericum patulum, Structural determination, Cytotoxicity

Yu-Feng Qiu, Yi Zhou, Cheng Chen, Juan Huang, Xing-Wei Yang. Prenylated acylphloroglucinols from the fruits of Hypericum patulum[J]. Natural Products and Bioprospecting, 2026, 16(4): 57-57.

Yu-Feng Qiu, Yi Zhou, Cheng Chen, Juan Huang, Xing-Wei Yang. Prenylated acylphloroglucinols from the fruits of Hypericum patulum[J]. 应用天然产物, 2026, 16(4): 57-57.

References

[1] Yang XW, Grossman RB, Xu G. Research progress of polycyclic polyprenylated acylphloroglucinols. Chem Rev. 2018;118(7):3508-58.
[2] Ciochina R, Grossman RB. Polycyclic polyprenylated acylphloroglucinols. Chem Rev. 2006;106(9):3963-86.
[3] Li XW, Li J, Stevens P. Flora of China. Beijing: Science Press; 1990. p. 25.
[4] State Administration of Traditional Chinese Medicine of the People’s Republic of China, Chinese Materia Medica, Shanghai Scientific and Technical Publishers, Shanghai. 1999;9:594-608.
[5] Ishiguro K, Nagareya N, Suitani A, Fukumoto H. A prenylated xanthone from cell suspension cultures of Hypericum patulum. Phytochemistry. 1997;44(6):1065-6.
[6] Tanaka N, Yano Y, Tatano Y, Kashiwada Y. Hypatulins A and B, meroterpenes from Hypericum patulum. Org Lett. 2016;18:5360-3.
[7] Liu YY, Ao Z, Xue GM, Wang XB, Luo JG, Kong LY. Hypatulone A, a homoadamantane-type acylphloroglucinol with an intricately caged core from Hypericum patulum. Org Lett. 2018;20:7953-6.
[8] Liu YY, Ao Z, Xu QQ, Zhu DR, Chen C, Wang XB, et al. Hyperpatulols A-I, spirocyclic acylphloroglucinol derivatives with anti-migration activities from the flowers of Hypericum patulum. Bioorg Chem. 2019;87:409-16.
[9] Wu ZN, Niu QW, Zhang YB, Luo D, Li QG, Li YY, et al. Hyperpatulones A-F, polycyclic polyprenylated acylphloroglucinols from Hypericum patulum and their cytotoxic activities. RSC Adv. 2019;9:7961-6.
[10] Tanaka N, Niwal K, Yano Y, Kashiwada Y. Prenylated benzophenone derivatives from Hypericum patulum. J Nat Med. 2020;74:264-8.
[11] Ao Z, Liu YY, Lin YL, Chen XL, Chen K, Kong LY, et al. Hyperpatulones A and B, two new peroxide polyprenylated acylphloroglucinols from the leaves of Hypericum patulum. Tetrahedron Lett. 2020;61:151385.
[12] Jia XY, Wu YM, Lei C, Yu YY, Li JQ, Li JY, et al. Hyperinoids A and B, two polycyclic meroterpenoids from Hypericum patulum. Chin Chem Lett. 2020;31:1263-6.
[13] Ye YS, Jiang NN, Yang XW, Xu G. Polycyclic polyprenylated acylphloroglucinol with an unprecedented spirocyclic core from Hypericum patulum. Chin Chem Lett. 2020;31:2433-6.
[14] Ye YS, Du SZ, Jiang NN, Xu HX, Yang J, Fu WW, et al. Novel meroterpenoids from Hypericum patulum: highly potent late Na_v1.5 sodium current inhibitors. Org Lett. 2020;22:6339-43.
[15] Zhang YX, Ao Z, He YW, Lu JY, Chen XL, Kong LY, et al. Hyperpatulones C-G, new spirocyclic polycyclic polyprenylated acylphloroglucinols from the leaves of Hypericum patulum. Fitoterapia. 2021;155:105063.
[16] Duan YL, Deng YF, Bu PF, Xie SS, Guo Y, Shi ZY, et al. Discovery of nor-bicyclic polyprenylated acylphloroglucinols possessing diverse architectures with anti-hepatoma activities from Hypericum patulum. Bioorg Chem. 2021;111:104902.
[17] Zhang F, Yang J, Yi P, Li YN, Hao XJ, Yuan CM. Hyperpatone A, a polycyclic polyprenylated acylphloroglucinol with a rare 8/6/5/6/5 pentacyclic skeleton from Hypericum patulum. Org Biomol Chem. 2023;21:140-6.
[18] Yang XW, Deng X, Liu X, Wu CY, Li XN, Wu B, et al. Hypercohin A, a new polycyclic polyprenylated acylphloroglucinol possessing an unusual bicyclo[5.3.1]hendecane core from Hypericum cohaerens. Chem Commun. 2012;48(48):5998-6000.
[19] Luo Y, Grossman RB, Nie XB, Yang XW. Total synthesis and structural reassignment of garcinielliptone FC, a polycyclic polyprenylated acylphloroglucinol with diverse bioactivity. Chem Commun. 2023;59(41):6215-8.
[20] Yang XW, Ding Y, Zhang JJ, Liu X, Yang LX, Li XN, et al. New acylphloroglucinol derivatives with diverse architectures from Hypericum henryi. Org Lett. 2014;16(9):2434-7.
[21] Hu YL, Hu K, Kong LM, Xia F, Yang XW, Xu G. Norascyronones A and B, 2,3,4- nor-polycyclic polyprenylated acylphloroglucinols from Hypericum ascyron. Org Lett. 2019;21(4):1007-10.
[22] Yang XW, Grossman RB. Revision of the structure of hypatulone A by NMR, computations, and biosynthetic considerations. Org Lett. 2020;22(2):760-3.
[23] Yang XW, Li MM, Liu X, Ferreira D, Ding Y, Zhang JJ, et al. Polycyclic polyprenylated acylphloroglucinol congeners possessing diverse structures from Hypericum henryi. J Nat Prod. 2015;78(4):885-95.
[24] Yang XW, Yang J, Xu G. Skeleton reassignment of type C polycyclic polyprenylated acylphloroglucinols. J Nat Prod. 2017;80(1):108-13.
[25] Grossman RB, Yang XW. Structural revision of garcinielliptin oxide and garcinielliptone E. J Nat Prod. 2020;83(6):2041-4.
[26] Wang X, Nie XB, Grossman RB, Ji TF, Yang XW. Structural revision of hyperibrin B and hyperscabrones H and I by biosynthetic considerations, NMR analysis, and chemical synthesis. J Nat Prod. 2021;84(7):2059-64.
[27] Xu ZH, Grossman RB, Qiu YF, Luo Y, Lan T, Yang XW. Polycyclic polyprenylated acylphloroglucinols bearing a lavandulyl-derived substituent from Garcinia xanthochymus fruits. J Nat Prod. 2022;85(12):2845-55.
[28] Qiu YF, Grossman RB, Yang XW. Structure revision of type B polycyclic polyprenylated acylphloroglucinols fused to a partly reduced furan ring. J Nat Prod. 2023;86(10):2391-7.
[29] Xu ZH, Luo Y, Qiu YF, Yang XW, Lan T. Prenylated acylphloroglucinols from the fruits of Garcinia xanthochymus. Fitoterapia. 2023;165:105427.
[30] Fu Y, Huang YQ, Xu Z, Liu X, Yang XW. Polyprenylated acylphloroglucinols from Garcinia species and structural revision of seven analogues. Nat Prod Bioprospect. 2025;15:34.
[31] Huang JC, Sheng L, Zong JF, Zhou YB, Li J, Hou AJ. Enantiomeric pairs of meroterpenoids with 11/5/6 spiro-heterocyclic systems from Hypericum kouytchense. Org Chem Front. 2022;9(23):6475-83.
[32] Zhang JJ, Yang XW, Ma JZ, Ye Y, Shen XL, Xu G. Cytotoxic polyprenylated acylphloroglucinol derivatives from Hypericum henryi. Tetrahedron. 2015;71:8315-9.
[33] 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.
[34] Jiang NN, Yue GGL, Li P, Ye YS, Gomes AJ, Kwok FHF, 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.
[35] Sun H, Wang J, Zhen B, Wang X, Suo X, Lin M, et al. Polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum pseudohenryi. Phytochemistry. 2021;187:112761.
[36] Hashida W, Tanaka N, Kashiwada Y, Sekiya M, Ikeshiro Y, Takaishi Y. Tomoeones A-H, cytotoxic phloroglucinol derivatives from Hypericum ascyron. Phytochemistry. 2008;69:2225-30.
[37] Abe S, Tanaka N, Kobayashi J. Prenylated acylphloroglucinols, chipericumins A-D, from Hypericum chinense. J Nat Prod. 2012;75(3):484-8.
[38] Tala MF, Talontsi FM, Zeng GZ, Wabo HK, Tan NH, Spiteller M, et al. Antimicrobial and cytotoxic constituents from native Cameroonian medicinal plant Hypericum riparium. Fitoterapia. 2015;102:149-55.
[39] Zhang JJ, Yang XW, Ma JZ, Liu X, Yang LX, Yang SC, et al. Hypercohones D-G, new polycyclic polyprenylated acylphloroglucinol type natural products from Hypericum cohaerens. Nat Prod Bioprospect. 2014;4:73-9.
[40] Zhou X, Xu WJ, Li YR, Zhang MH, Tang PF, Lu WJ, et al. Anti-inflammatory, antioxidant, and anti-nonalcoholic steatohepatitis acylphloroglucinol meroterpenoids from Hypericum bellum flowers. J Agric Food Chem. 2021;69:646-54.
[41] Zhou ZB, Li ZR, Wang XB, Luo JG, Kong LY. Polycyclic polyprenylated derivatives from Hypericum uralum: neuroprotective effects and antidepressant-like activity of uralodin A. J Nat Prod. 2016;79:1231-40.
[42] Ye Y, Yang XW, Zhou Y, Xu G. Homo-adamantane type polycyclic polyprenylated acylphloroglucinols from Hypericum hookerianum. Fitoterapia. 2019;133:43-50.
[43] Zhou ZB, Zhang YM, Pan K, Luo JG, Kong LY. Cytotoxic polycyclic polyprenylated acylphloroglucinols from Hypericum attenuatum. Fitoterapia. 2014;95:1-7.
[44] Hu LH, Sim KY. Sampsoniones C-H, a unique family of polyprenylated benzophenone derivatives with the novel tetracyclo[7.3.1.1^3,11.0^3,7]tetradecane-2,12,14-trione skeleton, from Hypericum sampsonii (Guttiferae). Tetrahedron Lett. 1999;40:759-62.
[45] Lin YL, Wu YS. Polyprenylated phloroglucinol derivatives from Hypericum sampsonii. Helv Chim Acta. 2003;86:2156-63.
[46] Zeng YH, Osman K, Xiao ZY, Gibbons S, Mu Q. Four geranyl-bearing polyisoprenylated benzoylphloroglucinol derivatives from Hypericum sampsonii. Phytochem Lett. 2012;5:200-5.
[47] Zhang JS, Zou YH, Guo YQ, Li ZZ, Tang GH, Yin S. Polycyclic polyprenylated acylphloroglucinols: natural phosphodiesterase-4 inhibitors from Hypericum sampsonii. RSC Adv. 2016;6:53469-76.

Prenylated acylphloroglucinols from the fruits of Hypericum patulum

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