Polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum perforatum and absolute configurations assignment of previously reported analogues
Graphical abstract
Introduction
Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a group of acylphloroglucinol derivatives featured by highly oxygenated acylphloroglucinol cores, which were densely decorated with isoprenyl or geranyl moieties [1], [2]. Since the first PPAP has been isolated from Hypericum perforatum L. (St. John’s wort) in 1971 [3], [4], this class of natural products have been extensively investigated because of their intricate molecular structures [5], [6], [7], [8], [9] and diverse biological activities [10], [11], [12], [13]. As the most famous medicinal herb from the genus of Hypericum, St. John’s wort has been used to treat depression in Europe for a long time due to its potent antidepressive activity on mild-moderate depression [14], [15], [16], [17], [18]. In recent years, St. John’s wort has also attracted broad interest for its pharmacological activities on neurological and immunological diseases [19], [20], [21].
Previous phytochemical investigations on H. perforatum by our group demonstrated that this plant is also a rich source of PPAPs [22], [23]. PPAPs are usually obtained as oils or gums, which were difficult to determine their absolute configurations by single-crystal method. In this study, thirteen undescribed PPAPs (1–13) were isolated from H. perforatum (Fig. 1) and their structures and absolute configurations were determined by extensive spectroscopic analyses. Furthermore, the absolute configurations of four previously reported analogues, garsubellins D and C [24] as well as garcinielliptones L and M [25], were assigned for the first time by NMR spectra analyses and OR calculations. The immunosuppressive activities and neuroprotective activities of selected compounds were also reported.
Section snippets
General
Optical rotations were determined by a PerkinElmer 341 polarimeter (PerkinElmer Inc., Fremont, California, USA). UV spectra were recorded on a Lambda 35 instrument (PerkinElmer Inc., Fremont, California, USA). ECD spectra were determined on a JASCO-810 spectrometer (JASCO, Tokyo, Japan). IR spectra were obtained using a Bruker Vertex 70 FT-IR spectrophotometer (Bruker, Karlsruhe, Germany). The NMR spectra were acquired on Bruker AM-400, AV-600, and AV-800 spectrometers, and the 1H and 13C NMR
Structure elucidation
Hyperformitin A (1) had the molecular formula of C35H52O6 based on its 13C NMR data and HRESIMS [M+Na]+ ion at m/z 591.3656 (calcd for 591.3656). The absorption bands of the IR spectrum exhibited the presence of hydroxy (3436 cm−1) and carbonyl (1722 cm−1) functionalities. The 1H NMR data (Table 2) showed signals of nine methyl singlets (δH 1.06–1.68, s), an isopropyl group (δH 1.13, d; 1.06, d; 2.64, sept), and four olefinic protons (δH 4.96–5.66). Analyses of the 13C and DEPT NMR data (Table 1
Conclusions
In summary, thirteen undescribed PPAPs (1–13) were isolated from Hypericum perforatum. Hyperformitins A–I (1–9) were featured by double-bond migration on the isoprenyl side chain. Their structures and absolute configurations were established by spectroscopic methods and the ECD spectra analysis. The absolute configurations of garsubellins D and C as well as garcinielliptones L and M were assigned for the first time by NMR spectra and specific rotations analyses together with OR calculations.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was financially supported by the Program for Changjiang Scholars of the Ministry of Education of the People's Republic of China (No. T2016088), the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021), the National Natural Science Foundation for Excellent Young Scholars (81922065), the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005), the National Natural Science Foundation of China (No. 21502057), the
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