Polycyclic Polyprenylated Acylphloroglucinol Derivatives Research Articles

Hyperacmosin N, new acylphloroglucinol derivative with complicated caged core from Hypericum acmosepalum

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins N–P (1–3), were isolated from the air-dried aerial parts of Hypericum asmosepalum. Especially, compound1possessed a rare hexacyclic core, which was formed via oxidation and radical cyclization. Their structures were established by NMR, HRMS (ESI), and experimental electronic circular dichroism (ECD) spectra. The plausible biogenetic pathways of1-3were proposed, which gave an insight for future biomimetic synthesis of the novel compounds.

Polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum pseudohenryi

Seven previously unidentified polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives hypseudohenrins A–G, along with six known analogs, were isolated from the aerial portion of Hypericum pseudohenryi. Their structures were determined by NMR, ECD and X-ray crystallographic spectroscopy. These compounds were screened for anti-inflammatory activity, and hypseudohenrins B and G (at the concentration of 10 μM) showed NO production inhibition ratios of 52.56% and 54.01%, respectively, which imply good anti-inflammatory activity. In particular, uraloidin A exhibited an NO inhibition ratio of 90.61%, while that ratio of the positive control compound dexamethasone was 94.88%. Additionally, anti-cancer and neural-protective activities were screened, but none of these compounds showed desirable activity.

Hypseudohenrins I − K: three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum pseudohenryi

Three previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) derivatives, hypseudohenrins I–K (1–3), along with a known analogue hyphenrone X (4), were isolated from the aerial part of Hypericum pseudohenryi. The structures of the new compounds were elucidated by NMR spectroscopy and ECD calculation. The anti-inflammatory activity of the compounds was evaluated. Compounds 1–3 showed mild anti-inflammatory activity while hyphenrone X showed prominent anti-inflammatory activity.

Hyperacmosins H-J, three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum acmosepalum

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1–3), with four known compounds (4–7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.

Polycyclic polyprenylated acylphloroglucinol derivatives with neuroprotective effects from Hypericum monogynum

A new polycyclic polyprenylated acylphloroglucinol (PPAP), hypermonin C (1), along with nine known PPAPs (2–10) were obtained from the leaves and twigs of Hypericum monogynum. The structures of the isolates were determined on the basis of extensive spectroscopic analysis. The neuroprotective effects of the isolates against several chemical-induced injuries in SH-SY5Y and PC12 cells were assessed, and most of the compounds exhibited significant protective effects at 10 μg/ml. Especially, three compounds (1, 3, and 7) showed excellent neuroprotective activity with a cell viability of 92.4% ∼ 95.8% in KCl-induced SH-SY5Y cell injury. Their preliminary structure-activity relationship was also discussed and the configuration of substituent in furohyperforin may be critical for the neuroprotective activity of PPAP derivatives.

Hyperascyrins L − N, rare methylated polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum ascyron

Seven natural compounds, including new compounds hyperascyrins L-N (1-3) and four known compounds (4-7), were acquired from the aerial parts of Hypericum ascyron, that were all identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). The structures of these compounds were established by NMR spectroscopy, experimental and calculated electronic circular dichroism (ECD) data. The neuroprotective activities and hepatoprotective activity of these compounds (10 µM) were evaluated. Compounds 1, 2 and 3 exhibited neuroprotection activity. Compounds 1 and 3 show hepatoprotective activity.

Polycyclic Polyprenylated Acylphloroglucinol Derivatives from Hypericum acmosepalum.

Hypericum acmosepalum belongs to the Hypericum genus of the Guttiferae family. The characteristic components in Hypericum are mainly a series of polycyclic polyprenylated acylphloroglucinols (PPAPs), flavonoids, and xanthones. Among them, the PPAPs have received much attention due to their novel structures and diverse pharmacological activities and have become hot spots in organic chemistry and medicinal chemistry. However, there are few reports about the chemical constituents of Hypericum acmosepalum at present, especially the PPAPs. This research is dedicated to the study of the air-dried aerial parts of Hypericum acmosepalum, which were extracted with 95% EtOH under reflux, then suspended and successively partitioned with petroleum ether and ethyl acetate. Five PPAP derivatives were obtained using various chromatographic techniques, and their structures were determined by NMR spectroscopic data, including two new phloroglucinol derivatives, hyperacmosin A (1) and hyperacmosin B (2). Those compounds were evaluated for their neuroprotective effect using two models.

Methylated Polycyclic Polyprenylated Acylphloroglucinol Derivatives from Hypericum ascyron.

Hyperascyrins A-H (1-11) and four known compounds (12-15) were acquired from the air-dried aerial parts of Hypericum ascyron and were all identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives. Their structures were established by NMR spectroscopy, experimental and calculated electronic circular dichroism (ECD) data, and comparison with established compounds. Compounds 8 and 9 showed protection against paracetamol-induced HepG2 cell damage at 10 μM. The neuroprotective activities of all compounds (10 μM) were evaluated, and compounds 1 and 8 exhibited mild neuroprotection against glutamate-induced toxicity in SK-N-SH cells.

Polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum scabrum

Three new polycyclic polyprenylated acylphloroglucinol derivatives (PPAPs), hyperibrins E–G (1–3), along with seven known compounds were identified from the air-dried aerial parts of Hypericum scabrum. Their structures were determined by NMR spectroscopic methods, both experimental and calculated electronic circular dichroism (ECD) spectra and comparison with known compounds. Compound 1 was derived from an analogue of compound 2 by cyclization, while a retro-Claisen reaction transformed another analogue of compound 2 into compound 3. Compounds 3, 4, 5, and 10 showed obvious hepatoprotective activities against paracetamol-induced HepG2 cell damage.

Four new prenylated phloroglucinol derivatives from Hypericum scabrum

Hyperibrins A−D (1–4), polycyclic polyprenylated acylphloroglucinol derivatives, were identified from air-dried aerial parts of Hypericum scabrum. All structures were determined by NMR spectroscopic methods and experimental and calculated ECD spectra. Compounds 1, 3, and 4 showed significant neuroprotective effects on glutamate-induced toxicity in SK-N-SH cells. Additionally, compounds 3 and 4 showed moderate hepatoprotective activities against paracetamol-induced HepG2 cell damage.

Cytotoxic polycyclic polyprenylated acylphloroglucinol derivatives and xanthones from Hypericum attenuatum

Two new polycyclic polyprenylated acylphloroglucinols, attenuatumione G (1) and attenuatumione H (2), together with five known compounds (3–7) have been isolated from the whole plant of Hypericum attenuatum. Their structures were elucidated by spectroscopic data including HRESIMS, 1D- and 2D-NMR. In biological assays, compound 2 showed moderate cytotoxic activities against Hep-G2 (IC50 9.11μM) and MCF-7 (IC50 16.24μM), compound 4 exhibited significant cytotoxic activity with IC50 value of 5.32μM against Hep-G2, and both compounds 5 and 6 revealed significant nitric oxide production inhibitory activity with IC50 values of 5.52 and 8.46μM, respectively.

Hypermongones A-J, Rare Methylated Polycyclic Polyprenylated Acylphloroglucinols from the Flowers of Hypericum monogynum.

Hypermongones A-J (1-10), rare methylated polycyclic polyprenylated acylphloroglucinol derivatives, together with three known simple acylphloroglucinols (11-13) as their plausible biogenetic precursors, were identified from the flowers of Hypericum monogynum. The structures of 1-10 were elucidated by analysis of their 1D and 2D NMR spectroscopic data; the absolute configuration of their polycyclic skeleton was determined by the electronic circular dichroism exciton chirality method and was subsequently confirmed by an X-ray diffraction study of 1. The evaluation of their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 cells revealed that compound 7 exhibited significant NO inhibition activity, with an IC50 value of 9.5 μM.

New acylphloroglucinol derivatives with diverse architectures from Hypericum henryi.

Hyphenrones A-F (1-6), six polycyclic polyprenylated acylphloroglucinol derivatives with four architectures including three unprecedented cores as exemplified by 1, 3, and 4, were isolated from Hypericum henryi. Compounds 3 and 4 possess two unique 5/8/5 and 6/6/5/8/5 fused ring systems, respectively. Their absolute configurations were defined by experimental and calculated ECD of 4 and X-ray diffractions of 5 and 6, coupled with their putative biosynthetic origins. Three compounds exhibited interesting AChE inhibitory activities.