Two novel tricyclic diterpenoids from Isodon rubescens var. taihangensis

Two novel tricyclic diterpenoids rubescensins U (1) and V (2) were isolated from the leaves of Isodon rubescens var. taihangensis. They were elucidated as a 8,15-seco-ent-kauranoid and an ent-abietanoid, respectively, by 1D and 2D NMR spectra, and single crystal X-ray analysis. Compound 1 is the first example of an 8,15-seco-ent-kaurane from the plants genus Isodon. A discussion of their biogenesis is described.     

3,4-seco-Diterpenoids from Trigonostemon flavidus

Phytochemical investigation on the stems of Trigonostemon flavidus resulted in the isolation of five new 3,4-seco-diterpenoids, trigoflavidones A-E (1-5), structurally related to the main co-occurring known 3,4-seco-sonderianic acid (6) and 3,4-seco-sonderianol (7). Compound 4 possesses new 3,4-seco rearranged ent-pimarane skeletal type, characteristic of a vinyl group at C-8, while 5 features a unique five-membered ring (C₁) fused with a cyclopropane ring (C₂). The structures of the new compounds were established by a combination of spectroscopic data and computational methods. Compounds 1-7 were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines.     

A new rearranged and a new seco-ent-kaurane diterpenoids from Isodon parvifolius

Parvifoline X (1), a new rearranged ent-kaurane diterpenoid, and parvifoline Y (2), a new 8,15-seco-ent-kaurane diterpenoid, were isolated from the leaves of Isodon parvifolius. Their structures were elucidated by spectroscopic methods including 2D NMR analysis, and supported by a biogenetic pathway. Parvifoline X (1), possessing a new 15(8→11)-abeo-7α,20-epoxy-ent-kaurane skeleton, was found from the genus Isodon for the first time. Compounds 1 and 2 were evaluated for their inhibitory activity against A549, HT-29, and K562 cell lines. Parvifoline Y (2) was the most cytotoxic against A549 cells with an IC₅₀ value of 4.97 μM.     

6,7-Seco-ent-kaurane-type diterpenoids from Isodon eriocalyx var. laxiflora

Twenty nine 6,7-seco-ent-kaurane-type diterpenoids including 18 new ones, laxiflorolides C–T (1–18), along with 21 known ones were obtained from Isodon eriocalyx var. laxiflora. Laxiflorolides E–G (3–5) are the first identified naturally occurring 6,7-seco-ent-kauranoids that feature a 3,6-epoxy unit, and laxiflorolide M (11) is the first identified naturally occurring 6-nor-6,7-seco-ent-kauranoid. The absolute configurations of compounds 1, 3, 6, and 11 were determined by single-crystal X-ray diffraction analyses. The cytotoxic activity of the isolates was evaluated by an MTT assay.     

Dracomolphesin A–E,five 3,4-seco-phenylpropanoids with Nrf2 inducing activity from Dracocephalum moldavica

Dracomolphesin A–E (1–5), five 3,4-seco-phenylpropanoids featuring an aromatic ring opened framework, were isolated from the aerial parts of Dracocephalum moldavica. The structures with absolute configurations were determined by spectroscopic methods coupled with Mosher method. Notably, these compounds represented an example of aromatic ring cleavage products of phenylpropanoids. The possible biosynthetic pathway of these compounds was proposed. Compounds 1, 2, 4 and 5 were demonstrated to be Nrf2 pathway activators.     

Secondary metabolites of the lichen-associated fungus Apiospora montagnei

The endolichenic fungus Apiospora montagnei isolated from the lichen Cladonia sp. was cultured on solid rice medium, yielding the new diterpenoid libertellenone L (1), the new pyridine alkaloid, 23-O-acetyl-N-hydroxyapiosporamide (2) and the new xanthone derivative 8-hydroxy-3-hydroxymethyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ether (3) together with 19 known compounds (4–22). The structures of the new compounds were elucidated by 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of the new 6,7-seco-libertellenone derivative 1 was determined by single-crystal X-ray diffraction. Four additional known compounds 23–26 were isolated when NaCl or NH₄Cl were added to solid rice medium. Compounds 7–9, 18 and 26 exhibited significant cytotoxicity against the L5178 murine lymphoma cell line with IC₅₀ values of 2.6, 0.2, 2.1, 2.7 and 1.7 μM, respectively.     

Phloroglucinol derivatives and a chromone glucoside from the leaves of Myrtus communis

Seven new phloroglucinol derivatives, myrtucommunins A–D (1–4), 6-methylisomyrtucommulone B (5), 4-methylmyrtucommulone B (6), and 2-isobutyryl-4-methylphloroglucinol 1-O-β-d-glucopyranoside (7), and one new chromone derivative, undulatoside A 6′-O-gallate (8), were isolated from the leaves of Myrtus communis (Myrtaceae). Myrtucommunins A–D (1–4) were conjugates of polymethylated acylphloroglucinol and flavonol rhamnoside. The absolute configurations of the rhamnosyl moieties for 1–4 were confirmed to be l in each case by HPLC analyses, while those of the aglycones were assigned by comparisons of the experimental and TDDFT calculated ECD spectra. 6-Methylisomyrtucommulone B (5) and 4-methylmyrtucommulone B (6) were assigned as 6/6/6 tricyclic acylphloroglucinol derivatives with a racemic nature. Antimicrobial activities of 1–8 and related known compounds were evaluated.     

Three novel 3,4-seco-podocarpane trinorditerpenoids from Aleurites moluccana

Three novel 3,4-seco-podocarpane-type trinorditerpenoids, moluccanic acid (1), moluccanic acid methyl ester (2), and 6,7-dehydromoluccanic acid (3), were isolated from the twigs and leaves of Aleurites moluccana. Their structures were elucidated by spectroscopic methods including 2D NMR analysis. The cytotoxicity of compounds 1-3 was evaluated.     

Aphanalides A–H,ring A-seco limonoids from the fruits of Aphanamixis polystachya

Eight new ring A-seco limonoids, aphanalides A–H (1–8) were isolated from the fruits of Aphanamixis polystachya. Aphanalides A–C (1–3) are the first examples of ring A-seco limonoids with an unusual oxetane ring between C-7 and C-14. The structures of aphanalide A (1) and aphanalide C (3) were confirmed by single-crystal X-ray studies. Their structures including absolute stereochemistry were established on the basis of extensive NMR spectroscopic analysis, by comparison of experimental and calculated electron circular dichroism (ECD) and by X-ray diffraction, representing the first report of assignment of absolute configuration of such type ring A-seco limonoids. The biogenetic origin of aphanalides A–D (1–4) from aphanalides E–H (5–8) was also postulated.     

Rhodauricanol A,an analgesic diterpenoid with an unprecedented 5/6/5/7 tetracyclic system featuring a unique 16-oxa-tetracyclo[11.2.1.01,5.07,13]hexadecane core from Rhododendron dauricum

A novel diterpenoid with an unprecedented 5/6/5/7 tetracyclic system, rhodauricanol A (1), five new grayanane-derived diterpenoids, dauricanols A?E (2?6), and five known ones (7?11) were isolated from the flowers of Rhododendron dauricum. Rhodauricanol A (1) possesses a unique 5/6/5/7 tetracyclic ring system featuring a 16-oxa-tetracyclo[11.2.1.0^1,5.0^7,13]hexadecane core. Dauricanols A?C (2?4) are the first 1,3-dioxolane conjugates of grayanane diterpenoids and 5-hydroxymethylfurfural and vanillin, respectively, and dauricanols D (5) and E (6) represent the first examples of 6-deoxy-1,5-seco-grayanane diterpenoids. Their structures were determined by spectroscopic methods, quantum chemical calculation including ¹³C NMR-DP4+ analysis and ECD calculation, and single-crystal X-ray diffraction analysis. Plausible biosynthetic pathways for 1?4 were proposed. All the isolates showed significant analgesic activities, and dauricanols B (3) and C (4) showed more potent analgesic activities than the positive control, morphine.     

seco-Polycyclic polyprenylated acylphloroglucinols with unusual carbon skeletons from Hypericum ascyron

Three new seco-polycyclic polyprenylated acylphloroglucinols (PPAPs), ascyronones A–C (1–3), and a new biosynthetic precursor, ascyronone D (4), were isolated from Hypericum ascyron together with three known analogues (5–7). Compounds 1 and 2, sharing an unusual seven-membered carbon core fused with a γ-lactone ring, could be derived from 1,9-seco-PPAPs via further rearrangement. A biomimetic transformation from 5 to 1 was performed by using base-driven retro-Claisen and rearrangement cascade reaction, which further confirmed the structure of 1 and shed light to its possible biosynthetic pathway. Interestingly, all these compounds are decorated with a methyl group at C-5 instead of a prenyl or geranyl group in many other PPAPs. The isolates were evaluated for their inhibitory activities against five human tumor cell lines.     

Meroterpenoids with diverse ring systems and dioxolanone-type secondary metabolites from Phyllosticta capitalensis and their phytotoxic activity

Twenty meroterpenoids with diverse ring systems including five new ones (1, 2, 5, 6, and 15), together with two new (23 and 24) and two known dioxolanone-type secondary metabolites were isolated from Phyllosticta capitalensis, an endophytic fungus from Cephalotaxus fortunei Hook. Compound 1 was the first example with a 9,14-seco ring A and a five-membered ring B in guignardone derivatives. Compound 2 represented a novel guignardone derivative possessing a 5/7/6/5 ring system with CH₂-7 attached to C-4 rather than C-6 in ring D. The structures of all new compounds were elucidated using spectroscopic data analyses and electronic circular dichroism comparison. The phytotoxic effects of compounds 1–24 on Lactuca sativa and Lolium perenne were evaluated. Compound 22 showed inhibition activity on the shoots growth of L. sativa and L. perenne, as well as the roots growth of L. perenne.     

Bisleuconins A-D: a pair of epimeric ent-kauranoid dimers and two new asymmetric analogues isolated from Isodonleucophyllus

A phytochemical investigation of Isodon leucophyllus led to the isolation of four novel ent-kauranoid dimers: bisleuconins A-D (1-4), and one known compound, rabdoloxin A (5). It was interesting that the structures of bisleuconins A (1) and B (2) were elucidated as a pair of epimeric ent-kauranoid dimers with unique linkage pattern C-16→C-17′ to connect two monomers. Bisleuconins C (3) and D (4) were two new asymmetric ent-kauranoid dimers. A possible biogenetic pathway of 1 and 2 was also proposed.     

Isolation and characterization of miscellaneous terpenoids of Schisandra chinensis

Two new bisnortriterpenoids with 18-norschiartane skeleton, wuweizidilactones G (1) and H (2), four new highly oxygenated nortriterpenoids based on a schisanartane skeleton, schindilactones D-G (3-6), a pre-schisanartane skeleton, pre-schisanartanin B (7), and a novel 3,4-seco-21,26-olide-artane triterpenoid wuweizilactone acid (8), along with 24 known terpenoids with different carbon frameworks, have been isolated from the acetone extract of the stems and leaves of Schisandra chinensis. The terpenoids produced by this plant have chemical diversity. The structures of new compounds 1-8 have been characterized by spectroscopic data interpretation. The cytotoxicity and anti-HIV-1 activity of all the Schisandra nortriterpenoids were evaluated.     

New lignan glycosides from Glehnia littoralis

From the roots ethanol extract of Glehnia littoralis, two new lignan glycosides, named glehlinoside E （1） and F （2）, were obtained. Their structures were determined to be （-）-secoisolariciresinol 4-O-β-D-（6-O-feruloyl） glucopyranoside （1） and （-）- secoisolariciresinol 4-O-f-β-D-（6-O-caffeloyl） glucopyranoside （2） by analysis of their spectral data, respectively.     

Officinatrione: an unusual (17S)-17,18-seco-lupane skeleton,and four novel lupane-type triterpenoids from the roots of Taraxacum officinale

Novel 5 lupane-type of triterpenois, i.e., 3β-acetoxy-18α,19α-epoxylupan-21β-ol (1), 18α,19α-epoxy-21β-hydroxylupan-3-one (2), lup-18-ene-3,21-dione (3), lupa-18,21-dien-3β-yl acetate (4), and (17S)-17,18-seco-lup-19(21)-ene-3,18,22-trione (5), named officinatrione, as well as 16 known compounds from the roots of Taraxacum officinale collected in Takatsuki city, Osaka, Japan. Of the above compounds, 5 was the first lupane-type triterpene, of which the D-ring was open to form a nine-membered ring. Compounds 2 and 5 exhibited moderate cytotoxic activities against L1210 cell line (IC₅₀ 10.5 and 10.1 μM).     

Further studies on the constituents of the gorgonian octocoral Pseudopterogorgia elisabethae collected in San Andrés and Providencia islands, Colombian Caribbean: isolation of a putative biosynthetic intermediate leading to erogorgiaene

Chemical investigations of the MeOH-CH₂Cl₂ extract of Pseudopterogorgia elisabethae specimens collected in the islands of San Andrés and Providencia, Colombian Caribbean, yielded four new diterpenes (1, 3, 5, 7) along with seco-pseudopterosin J (8), and amphilectosins A (9) and B (10). The structures of the new compounds were established through spectral studies as an elisabethatriene analog named elisabethatrienol (1), 10-acetoxy-9-hydroxy- and 9-acetoxy-10-hydroxy-amphilecta-8,10,12,14-tetraenes (isolated as an interconverting mixture) (3), amphilecta-8(13),11,14-triene-9,10-dione (5), and a seco-pseudopterosin 7-O-α-l-fucopyranoside named seco-pseudopterosin K (7). Elisabethatrienol can be regarded as a biosynthetic intermediate leading to erogorgiaene.     

Eight new limonoids from Turraea pubescens

Eight new ring B-seco limonoids, turrapubesic acids A-C (1-3) and turrapubesins C-G (4-8), along with turraflorin E and isoazadironolide were isolated from the twigs and leaves of Turraea pubescens. Turrapubesic acids A-C (1-3) are a group of ring B-seco limonoid 17-carboxylic acids with a new C₂₃ skeleton, and turrapubesin C (4) incorporates an unprecedented 1,30-oxygen bridge. The structures including absolute stereochemistry of 1-8 were established on the basis of extensive NMR spectroscopic analysis and CD study. The cytotoxicity of the isolates against the P-388 and A-549 cells was evaluated.     

Hyperbenzones A and B,two 1,2-seco and rearranged polycyclic polyprenylated acylphloroglucinols from Hypericum beanii

Two novel seco-polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbenzones A (1) and B (2), were isolated from the roots of Hypericum beanii, together with one known biosynthetic congener 3. Compound 1 incorporates a 6/5/5 ring system with an unprecedented spiro[bicyclo[3.3.0]octane-3,1?-cyclohexane]-2,2??dione motif. The structures of 1 and 2 were determined by a combination of high resolution electrospray ionization mass spectroscopy (HRESIMS), nuclear magnetic resonance (NMR) spectroscopic analyses, gage-independent atomic orbital (GIAO) NMR chemical shift calculation with DP4+ analyses, electronic circular dichroism (ECD) calculation, and X-ray diffraction analysis. A 1,2-seco retro-Claisen rearrangement from a bicyclo[3.3.1]nonane PPAP precursor and following chemodivergent radical cascade cyclizations are proposed as the key steps in the biosynthetic pathway to yield compounds 1 and 2. Biological investigations indicated that compounds 1 and 3 could decrease intracellular lipid accumulation in a palmitic acid-induced nonalcoholic steatohepatitis (NASH) cell model.