Discovery from Hypericum Elatoides and Synthesis of Hyperelanitriles As α-aminopropionitrile-containing Polycyclic Polyprenylated Acylphloroglucinols

Overview

Journal Commun Chem

Publisher Springer Nature

Specialty Chemistry

Date 2024 Jan 3

PMID 38167859

Authors

Jin-Yan Xie

Pengfei Li

Xi-Tao Yan

Jin-Ming Gao

Affiliations

Soon will be listed here.

Abstract

The search for lead compounds with anti-neuroinflammatory activity from structurally 'optimized' natural products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A-D (1-4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1-4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1-5.

Citing Articles

Three New Ionone Glycosides from Maxim.

Yang J, Zhu Y, Zeng Y, Li H, Li C, Gao J Molecules. 2024; 29(11).

PMID: 38893339 PMC: 11173609. DOI: 10.3390/molecules29112462.

Abietane-Type Diterpenoids from the Arils of .

Gao Y, Yang J, Zhang Y, Gao L, Tian J, Han W Molecules. 2024; 29(9).

PMID: 38731397 PMC: 11085307. DOI: 10.3390/molecules29091905.

Four New Polyprenylated Acylphloroglucinols from L.

Wang X, Liu W, Chen S, Gao Y, Tian J, Gao J Molecules. 2024; 29(8).

PMID: 38675576 PMC: 11052217. DOI: 10.3390/molecules29081756.

References

Xu Z, Grossman R, Qiu Y, Luo Y, Lan T, Yang X . Polycyclic Polyprenylated Acylphloroglucinols Bearing a Lavandulyl-Derived Substituent from Fruits. J Nat Prod. 2022; 85(12):2845-2855. DOI: 10.1021/acs.jnatprod.2c00888. View

Ciochina R, Grossman R . Polycyclic polyprenylated acylphloroglucinols. Chem Rev. 2006; 106(9):3963-86. DOI: 10.1021/cr0500582. View

Yan X, An Z, Huangfu Y, Zhang Y, Li C, Chen X . Polycyclic polyprenylated acylphloroglucinol and phenolic metabolites from the aerial parts of Hypericum elatoides and their neuroprotective and anti-neuroinflammatory activities. Phytochemistry. 2018; 159:65-74. DOI: 10.1016/j.phytochem.2018.12.011. View

Zhang N, Shi Z, Xu Q, Sun W, Gu L, Xie S . Longisglucinols A-C, Structurally Intriguing Polycyclic Polyprenylated Acylphloroglucinols with Anti-inflammatory Activity from . Org Lett. 2020; 22(20):7926-7929. DOI: 10.1021/acs.orglett.0c02853. View

Kou R, Gao Y, Xia B, Wang J, Liu X, Tang J . Ganoderterpene A, a New Triterpenoid from , Attenuates LPS-Induced Inflammation and Apoptosis via Suppressing MAPK and TLR-4/NF-κB Pathways in BV-2 Cells. J Agric Food Chem. 2021; 69(43):12730-12740. DOI: 10.1021/acs.jafc.1c04905. View

Guttroff C, Baykal A, Wang H, Popella P, Kraus F, Biber N . Polycyclic Polyprenylated Acylphloroglucinols: An Emerging Class of Non-Peptide-Based MRSA- and VRE-Active Antibiotics. Angew Chem Int Ed Engl. 2017; 56(50):15852-15856. DOI: 10.1002/anie.201707069. View

Tang J, Huang L, Deng J, Wang Y, Guo C, Peng X . Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone in 5xFAD Alzheimer's disease mice model. Redox Biol. 2022; 50:102229. PMC: 8760418. DOI: 10.1016/j.redox.2022.102229. View

Leger S, Bayly C, Black W, Desmarais S, Falgueyret J, Masse F . Primary amides as selective inhibitors of cathepsin K. Bioorg Med Chem Lett. 2007; 17(15):4328-32. DOI: 10.1016/j.bmcl.2007.05.024. View

Zhang R, Ji Y, Zhang X, Kennelly E, Long C . Ethnopharmacology of Hypericum species in China: A comprehensive review on ethnobotany, phytochemistry and pharmacology. J Ethnopharmacol. 2020; 254:112686. DOI: 10.1016/j.jep.2020.112686. View

10.

Zeng Y, Yuan C, Li Y, Huang L, Hu Z, Gu W . Hymoins A-D: Two Pairs of Polyprenylated Acylphloroglucinols from and Their Light-Induced Transformation. Org Lett. 2021; 23(8):3125-3129. DOI: 10.1021/acs.orglett.1c00811. View

11.

Yan X, An Z, Tang D, Peng G, Cao C, Xu Y . Hyperelatosides A-E, biphenyl ether glycosides from , with neurotrophic activity. RSC Adv. 2022; 8(47):26646-26655. PMC: 9083129. DOI: 10.1039/c8ra05322g. View

12.

Huang L, Zhang Z, Li Y, Yi P, Gu W, Yang J . Hypersampones A-C, Three Nor-Polycyclic Polyprenylated Acylphloroglucinols with Lipid-Lowering Activity from . Org Lett. 2022; 24(32):5967-5971. DOI: 10.1021/acs.orglett.2c02240. View

13.

Xie J, Wang Z, Liu W, Liu H, Li D, Sang Y . Hyperelatolides A-D, Antineuroinflammatory Constituents with Unusual Carbon Skeletons from . J Nat Prod. 2023; 86(8):1910-1918. DOI: 10.1021/acs.jnatprod.3c00226. View

14.

Yang X, Grossman R, Xu G . Research Progress of Polycyclic Polyprenylated Acylphloroglucinols. Chem Rev. 2018; 118(7):3508-3558. DOI: 10.1021/acs.chemrev.7b00551. View

15.

Camacho C, Pizzio M, Roces D, Boggian D, Mata E, Bellizzi Y . Design, synthesis and cytotoxic evaluation of a library of oxadiazole-containing hybrids. RSC Adv. 2022; 11(47):29741-29751. PMC: 9040754. DOI: 10.1039/d1ra05602f. View