(±)-Walskiiglucinol A, a pair of rearranged acylphloroglucinol derivative enantiomers from Hypericum przewalskii.

(±)-Walskiiglucinol A (1a/1b), a pair of rearranged acylphloroglucinol derivatives with a new carbon skeleton, was obtained from Hypericum przewalskii. Compounds 1a/1b were the first examples of naturally occurring acylphloroglucinol derivatives possessing a unique 1-oxaspiro[4.4]nonane core bearing a new 5/5 ring system. Their planar and relative structures were identified by extensive spectroscopic analysis and NMR chemical shift calculations with DP4+ probability analysis, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. A plausible biogenetic pathway of 1a/1b was proposed in which the breakage of the C-2/C-3 linkage via a retro-Claisen reaction and the cyclization between C-3 and C-1 were proposed as key steps. The isolates were evaluated for cytotoxic activities against a panel of cancer cell lines and anti-inflammatory activities against lipopolysaccharide (LPS)-induced NO production, and compounds 1a/1b showed moderate cytotoxic activities with IC50 values ranging from 9.72 to 36.75 µM.

Norprzewalsone A, a Rearranged Polycyclic Polyprenylated Acylphloroglucinol with a Spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] Core from Hypericum przewalskii.

Norprzewalsone A (1), a rearranged polyprenylated polycyclic acylphloroglucinol (PPAP) with a new carbon skeleton, along with a new congener, norprzewalsone B (2), were isolated from Hypericum przewalskii. Compound 1 possessed a new 5/6/5/6/6 pentacyclic ring system based on a spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] core, which might be derived from the common [3.3.1]-type bicyclic polyprenylated acylphloroglucinol (BPAP) via the key retro-Claisen, intramolecular cyclization, and Diels-Alder cyclization reactions. Their structures and absolute configurations were confirmed by spectroscopic data, calculated 1D NMR data with DP4+ probability analyses, and electronic circular dichroism calculations and comparison. More significantly, compound 1 exhibited a moderate inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells.

Kiiacylphnols A-H, eight undescribed polycyclic polyprenylated acylphloroglucinols with anticancer activities from Hypericum przewalskii Maxim.

Kiiacylphnols A-H, eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs), along with two known congeners (hyperforcinol F and oxepahyperforin), were obtained from Hypericum przewalskii Maxim. The structures of these metabolites were confirmed by spectroscopic analyses, quantum-chemical 1H and 13C NMR calculations with DP4+ analyses, electronic circular dichroism (ECD) comparisons and calculations. Kiiacylphnols A and B were the first [3.3.1]-type PPAPs with an unusual octahydrooxireno[2,3-i]chromene scaffold bearing a rare 6/6/6/3 ring system. More significantly, kiiacylphnol A and oxepahyperforin displayed cytotoxicity against acute myeloid leukemia and diffuse large B-cell lymphoma cell lines by inducing cell apoptosis.

Discovery of bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum wilsonii.

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperwilsones A-K (1-11), along with five known PPAPs (12-16), were isolated from Hypericum wilsonii. Their structures were established via spectroscopic methods, the careful analysis of calculated and experimental electronic circular dichroism (ECD) spectra, single-crystal X-ray diffraction, the modified Mosher's method, and [Rh2(OCOCF3)4]-induced ECD. Hyperwilsone A (1) and hyperwilsone B (2) possessed the unique acetal functionality. Hyperwilsone C (3) was a rare example of [3.3.1]-type PPAP possessing a 3-isopropylfuran moiety. In bioassay, compounds 9 and 10 showed potent anti-inflammatory activity against LPS-induced NO production by inhibiting the nuclear translocation of NF-κB p65 and thus reducing the production of proinflammatory cytokines. Compounds 5, 8, 11, and 14 exhibited moderate inhibitory activity against SUDHL-4 and HL60 cancer cells with IC50 values in the range of 5.74-19.82 µM.

(±)-hyperzewalsins A-D, four pairs of nor-monocyclic polyprenylated acylphloroglucinols with immunosuppressive activity from hypericum przewalskii maxim.

Three pairs of previously undescribed 2,3-nor-monocyclic polyprenylated acylphloroglucinols (MPAPs), (±)-hyperzewalsins A-C, a pair of 1,2,3,4-nor-MPAPs, (±)-hyperzewalsins D, along with one undescribed precursor, hyperzewalsin E, were isolated and identified from the aerial parts of Hypericum przewalskii Maxim. (Hypericaceae), and their structures were confirmed by extensive spectroscopic analyses, and quantum-chemical calculations including electronic circular dichroism calculations and NMR calculations with a DP4+ analysis. Significantly, (±)-hyperzewalsins A-D represented the first nor-MPAPs bearing carbon chain constitutions based on diverse highly degraded phloroglucinols. (±)-Hyperzewalsins A-C were the rare nor-MPAPs characterized by degradations of C-2 and C-3 in the core decorated by scissions of C-3/C-4 and C-1/C-2 bonds through Retro-Claisen reactions. (±)-Hyperzewalsins D were the first examples of naturally occurring MPAPs with the loss of C-1/2/3/4 in the phloroglucinol ring formed by cleavages of C-3/C-4 and C-1/C-6 bonds via Retro-Claisen and decarboxylation reactions. Plausible biogenetic pathways for the isolates were proposed. The isolates were evaluated for their immunosuppressive activity in lipopolysaccharide-stimulated murine splenocytes.

Hypaluton A, an Immunosuppressive 3,4-nor-Polycyclic Polyprenylated Acylphloroglucinol from Hypericum patulum.

Hypaluton A (1), an unprecedented nor-polycyclic polyprenylated acylphloroglucinol (PPAP) bearing a new 8/6 bicyclic architecture, along with a new congener, hypaluton B (2), was obtained from Hypericum patulum. Their structures were confirmed by spectroscopic analyses, quantum-chemical 13C NMR calculations, electronic circular dichroism comparisons, and calculations. Hypaluton A is the first PPAP possessing an unparalleled 3,4-nor-bicyclic polyprenylated acylphloroglucinol (BPAP) scaffold, which might be derived from the common [5.3.1]-type-BPAP by losing seven carbons (C-3/4 of the acylphloroglucinol core and the isoprenyl at C-3) via the breakage at C-4-C-5 and C-2-C-3 bonds in the acylphloroglucinol core, together with the benzoyl migration through the hemiketalization/retro-Claisen cascade. More significantly, compound 1 is also the first discovered [6.3.0]-PPAP, which displayed pronounced inhibitory activity against lipopolysaccharide-induced B lymphocyte proliferation.

Discovery of nor-bicyclic polyprenylated acylphloroglucinols possessing diverse architectures with anti-hepatoma activities from Hypericum patulum.

Five new 2-nor-bicyclic polyprenylated acylphloroglucinols (BPAPs), norhyperpalums A-E (1-5), three new 2,3-nor-BPAPs, norhyperpalums F-H (8-10), one new 2,3,4-nor-BPAP (13), and four known analogs (6, 7, 11 and 12) were obtained from Hypericum patulum. Their structures were confirmed by spectroscopic data, electronic circular dichroism (ECD) calculations and comparisons, quantum-chemical 13C NMR calculations with DP4 + probability analysis, the modified Mosher's method, Rh2(OCOCF3)4-induced ECD, and X-ray crystallographic data. Norhyperpalums A-E (1-5) are rare 2-nor-BPAPs bearing a 6/5/5 system based on a hexacyclic-fused 1,6-dioxaspiro[4.4]nonane core, and norhyperpalums F and G (8 and 9) exhibit an unusual 6-oxabicyclo[3.2.1]octane architecture. More significantly, compound 2 displayed pronounced cytotoxicities against hepatoma cell lines by the induction of S-phase cell cycle arrest and promotion of cell apoptosis.