Epimeric Pairs Research Articles

Halogenated meroterpenoids with antifungal activities from the Deep-Sea-Derived fungus Acremonium sclerotigenum guided by the genomic and OSMAC strategy.

Thirteen new meroterpenoids, acremorins A-M (1, 2, 4, 6, 7 and 9-16), together with three known analogues (3, 5 and 8) were isolated from the deep-sea-derived fungus Acremonium sclerotigenum LW14 guided by the genomic and OSMAC strategy. Their structures and absolute configurations were established by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculations, Rh2(OCOCF3)4-induced ECD experiments, and a single-crystal X-ray diffraction experiment. Compounds 2, 4, 6 and 9 represent the rare brominated ascochlorins. Compounds 1/3 and 2/4 are two pairs of epimers isomerized at C-19. Compounds 1 and 2 are the first examples of ascochlorins which have the 19S configuration in the cyclohexanone moiety. Compounds 3/7, 8/10 and 11/12 are three pairs of epimers isomerized at C-12, C-18 and C-15, respectively. Compounds 7-10 showed moderate antifungal activity against Cryptococcus gattii 3271G1 with the same MIC values of 8μg/mL. The treatment with compound 7 led to a significant reduction in the cell wall thickness, rarefaction of cytoplasm, and damage to the structural integrity of organelles in C. gattiii 3271G1. Further RNA sequencing (RNA seq) analysis indicated that compound 7 exerted its anti-C. gattiii effect by up-regulating the biosynthesis and RNA binding of ribosomes, while concurrently inhibiting RNA and nucleic acid metabolism and ATPase activity.

Spirocyclic iridoid alkaloids from Plumeria rubra.

Plumerianoids A-D (1-4) with a new intact spirocyclic iridoid alkaloid skeleton, along with a new degraded alkaloid 8-epi-plumerianine (5), and a known one (6), were isolated and characterized from Plumeria rubra. The structure of 6 was revised as (8R,13S)-plumerianine. These alkaloids consist of three epimeric pairs (1/2, 3/4, and 5/6), exhibiting virtually identical NMR spectra within each pair. Furthermore, the electronic circular dichroism (ECD) curves of each epimeric pair are roughly mirror-like, reminiscent of enantiomers. This study calls for attention on the structural elucidation of special compound classes when the associated chiral centers are far away from the chromophores and/or at the terminal of the molecules. In addition, compound 3 exhibited moderate antiplasmodial activity.

Metabolic transformation of paralytic shellfish toxins in the mussel Mytilus galloprovincialis under different exposure modes

Gymnodinium catenatum is a widely distributed toxic marine dinoflagellate that produces paralytic shellfish toxins (PSTs). It is prone to causing algal blooms and poses a serious threat to the shellfish industry and human health. Previous studies have shown that when algal blooms occur, shellfish can accumulate PSTs in their bodies due to filtration. In this study, mussels (Mytilus galloprovincialis) were fed with G. catenatum at different fixed or varied cell density over time, with the latter designed to mimic the changes in algal cell density over time in the wild. The PST concentration in the mussels was positively correlated with the number of algal cells, and PSTs rapidly accumulated in the mussels under both feeding modes. Compared with constant feeding in the low feeding group, variable cell density feeding over time was more conducive to the accumulation of PSTs in M. galloprovincialis. An obvious toxin transformation process was also detected in the mussels, which transformed the less toxic gonyautoxins-5 and -6 and N-sulfocarbamoyl gonyautoxin-3 ingested from G. catenatum into the more toxic decarbamoyl gonyautoxin-2, decarbamoyl saxitoxin, and decarbamoyl neosaxitoxin. The ratio of epimer pairs, α:β, tended to stabilize when the toxin concentration was highest, and it increased rapidly after mussels stopped consuming toxigenic algae. These results suggested that the formation of α-stable toxoids mainly occurred during the process of toxin depuration. Toxins were also transformed from low to high toxicity, and α-stable toxoids were formed mainly in the hepatopancreas. These results provided basic data for better understanding of the laws governing metabolic transformation of PSTs in bivalves during algal blooms.

Multioxidized polyketides from an endophytic Penicillium sp. YUD17006 associated with Gastrodia elata

Three novel, highly oxygenated polyketides, multioketides A−C (1−3), and three previously described multioxidized aromatic polyketides (4−6), were isolated from an endophytic Penicillium sp. YUD17006 associated with Gastrodia elata. Their chemical structures were elucidated using extensive spectroscopic data, electronic circular dichroism calculations, and single X-ray diffraction analysis. All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation. Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core. Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities. Plausible biosynthetic pathways for 1−6 were proposed. Additionally, compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyrosine phosphatase 1B.

A new flavan-3-ol from Sargentodoxae Caulis

Sargentodoxae Caulis was extracted with 80% ethanol and separated by macroporous resin, MCI, and ODS column chromatography and semi-preparative high performance liquid chromatography. The structures of the compounds were identified based on the NMR and MS data. A total of 19 compounds were identified as parabaroside D(1),(R)-2-(3,4-dihydroxyphenyl)-2-hydroxyethyl-O-β-D-glucopyranoside(2),(S)-2-(3,4-dihydroxyphenyl)-2-hydroxyethyl-O-β-D-glucopyranoside(3), protocatechin-3-O-β-D-glucoside(4), p-hydroxybenzoate-β-D-glucopyranoside(5), gentisic-5-O-β-D-glucopyranoside(6), vanillic acid 4-O-β-D-glucoside(7), syringic acid glucoside(8), uracil(9), uridine(10), neochlorogenic acid(11), chlorogenic acid(12), cryptochlorogenic acid(13), 3,4-dihydroxyphenylethanol glucoside(14), cuneataside A(15), cuneataside C(16), 4-hydroxy-3-methoxyacetophenone-4-O-β-D-apiose-(1→6)-β-D-glucopyranoside(17), proanthocyanidin B2(18), and baimantuoluoamide B(19). Compound 1 was a new flavan-3-ol, and compounds 2, 3, 5, 6, 9, and 19 were isolated from this plant for the first time. Compounds 2 and 3 were a pair of epimers. Compound 14 had the highest anti-inflammatory activity.

Self-assembly variation of glycyrrhetinic acid epimers: Assembly mechanism and antibacterial efficacy between 18 α-GA and 18 β-GA

Studies have confirmed that the spatial arrangement of chiral molecules has a decisive influence on supramolecular assembly. However, the effect of epimerization caused by the change of a single chiral center on the self-assembly of chiral molecules has not been reported. Herein, we explored a pair of epimers 18 α-glycyrrhetinic acid and 18 β-glycyrrhetinic acid from Glycyrrhiza uralensis Fisch, which had completely different medicinal activities. In this study, we found that these epimers of glycyrrhetinic acid showed distinct self-assembly properties under the condition of the deionized water and a small amount of DMSO solution. Interestingly, the cis-configured 18 β-GA could form a 'head-to-tail' interlaced structure and further self-assembled to form nanoparticles, while trans-configured 18 α-GA was connected in a “head-to-head” manner, and due to the excessive steric hindrance that made it difficult to assemble. This work not only clearly demonstrates the impact of epimerization due to changes in a single chiral center on the self-assembly of chiral molecules as well as biological activity, but also provides new insights into the self-assembly of natural organic molecules in the development of nanomedicines and biofunctional materials.

Tagpyrrollins A and B and Tagpyrrollidone A: Three Pyrrole Steroid Analogues with AKR1B1-Targeting Inhibitory Activity from the Sponges Stylissa massa and Pseudospongosorites suberitoides.

Pyrrole alkaloids (PAs) are a diverse class of natural products with complex carbon frameworks and broad bioactivities that are usually derived from marine sponges. Stylissa massa and Pseudospongosorites suberitoides are two independent sponges collected from the South China Sea in 2013 and 2018, respectively. We discovered PAs are common constituents in both two sponges; more specifically, S. massa produces pyrrole-imidazole alkaloids, and P. suberitoides contains pyrrolidone alkaloids. In this study, three pyrrole steroid metabolites were obtained. Compounds 1 and 2 are a pair of epimers sharing a new 5/7/5/6/6 pentacyclic structural configuration, and compound 3 has a new rigid 5/6/6 tricyclic structure. Interestingly, their scaffolds all possess a 6/6 bicyclic system on the featured classic pyrrole/pyrrolidone skeletons, so-dubbed tagpyrrollins A and B (1 and 2, respectively) and tagpyrrollidone A (3). From a biosynthetic viewpoint, 4,5-dihydroxypent-2-enal probably plays a crucial role in constructing these pyrrole steroid analogues. Based on our previous study on the inhibitory activity of spongiacidin targeting AKR1B1, a drug target for the treatment of chronic diabetic complications, in this study we found that tagpyrrolin A (1) also exhibits an inhibitory effect against AKR1B1.

Synthesis and Ring‐Closing Reactions of Aminocyclohexane Derivatives Bearing Unsaturated Side Chains at C2: Stereocontrolled Approaches to cis‐ and trans‐Fused Perhydro‐indoles and ‐Quinolines

AbstractTwo epimeric pairs of N‐Ts‐protected cyclohexylamines that incorporate an unsaturated side‐chain at the C2 position have been prepared. Contrary to expectations, none of these underwent clean, photochemically‐induced intramolecular hydroamination reactions to give the corresponding perhydro‐indole or ‐quinolines. However, they did participate in efficient olefin cross metathesis (OCM) reactions with methyl crotonate. Three of the four acrylates so‐formed engaged in base‐promoted and completely diastereoselective, intramolecular aza‐Michael addition (cyclization) reactions to give the isomeric and C2‐substituted perhydro‐indoles or ‐quinolines with the structures of these being confirmed by single‐crystal X‐ray analyses. DFT calculations generated results consistent with the observed diastereoselectivities and the proposed transition states. Manipulation of the ester groups associated with the cyclization products allowed for their conversion, inter alia, into the corresponding n‐propyl residues and thus providing novel analogues of neurotoxic alkaloids such as pumiliotoxin C.

A Pair of Epimers of Lignan Alleviate Neuroinflammatory Effects by Modulating iNOS/COX-2 and MAPK/NF-κB Signaling Pathways.

Neuroinflammation is a causative factor in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Previous studies have shown that Artemisia mongolica has anti-inflammatory properties. Aschantin (AM3) has been shown to have anti-inflammatory effects. However, the mechanism of AM3 and its epimer epi-aschantin (AM2) remains controversial. Therefore, the present study explored the mechanism of neuroinflammation by AM2 and AM3 and attempted to reveal the relationship between the structure of AM2 and AM3 and anti-neuroinflammatory activity. We isolated for the first time 12 lignans from A. mongolica that inhibited NO content at 10μM in LPS-stimulated BV2 cells. Among them, epi-aschantin (AM2) and Aschantin (AM3) showed significant inhibition in NO screening. With further studies, we found that both AM2 and AM3 effectively inhibited the overproduction of NO, PGE2, IL-6, TNF-α and MCP-1, as well as the overexpression of COX-2 and iNOS. Mechanistic studies have shown AM2 and AM3 significantly inhibited the phosphorylation of ERK, JNK and P-38 in the MAPK signaling pathway and p-IκBα,p-p65 and blocked p65 entry into the nucleus. The results suggested that the pair of epimers (AM2 and AM3) can be used as potential therapeutic agents in the treatment of various brain disorders and that structural differences do not differ in anti-neuroinflammatory effects.

Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024.

Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (-)-nigrosporine C (-)-3, together with eight known compounds (4-11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1-3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher's method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 μmol/L and without cytotoxicity in a concentration of 100.0 μmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 μmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 μmol/L.

Strukturelle Einblicke in die Terpencyclasedomänen Zweier Pilzlicher Sesterterpensyntasen und Enzymengineering zur Diversifizierung von Sesterterpenen

AbstractÜber die Strukturen und katalytischen Mechanismen von Sesterterpensynthasen (StTSs) ist wenig bekannt, was das strukturbasierte Engineering von StTSs zur Erweiterung der strukturellen Diversität von Sesterterpenen erheblich erschwert. Wir berichten hier über die Kristallstrukturen der Terpencyclisierungsdomänen (TC) von zwei pilzlichen StTSs: der Sesterfisherol‐Synthase (NfSS) und der Sesterbrasiliatrien‐Synthase (PbSS). Beide TC‐Strukturen enthalten Benzyltriethylammoniumchlorid (BTAC), Pyrophosphat (PPi) und Magnesiumionen (Mg2+), wodurch die katalytisch aktiven Zentren klar definiert sind. Eine Kombination aus Theorie und Experimenten, einschließlich der Modellierung carbokationischer Intermediate, ortsgerichteter Mutagenese und Isotopenmarkierungen, lieferte detaillierte Einblicke in die strukturellen Grundlagen der katalytischen Mechanismen. Strukturbasiertes Engineering von NfSS und PbSS führte zur Bildung von 20 Sesterterpenen, darunter 13 neue Verbindungen und vier Epimerpaare mit unterschiedlichen Konfigurationen an C18. Diese Ergebnisse erweitern die strukturelle Vielfalt von Sesterterpenen und liefern wichtige Erkenntnisse für die zukünftige Forschung im Bereich der synthetischen Biologie.

Structural Insights Into the Terpene Cyclization Domains of Two Fungal Sesterterpene Synthases and Enzymatic Engineering for Sesterterpene Diversification.

Little is known about the structures and catalytic mechanisms of sesterterpene synthases (StTSs), which greatly hinders the structure-based engineering of StTSs for structural diversity expansion of sesterterpenes. We here report on the crystal structures of the terpene cyclization (TC) domains of two fungal StTSs: sesterfisherol synthase (NfSS) and sesterbrasiliatriene synthase (PbSS). Both TC structures contain benzyltriethylammonium chloride (BTAC), pyrophosphate (PPi), and magnesium ions (Mg2+), clearly defining the catalytic active sites. A combination of theory and experiments including carbocationic intermediates modeling, site-directed mutagenesis, and isotope labeling provided detailed insights into the structural basis for their catalytic mechanisms. Structure-based engineering of NfSS and PbSS resulted in the formation of 20 sesterterpenes including 13 new compounds and four pairs of epimers with different configurations at C18. These results expand the structural diversity of sesterterpenes and provide important insights for future synthetic biology research.

Neuroprotective azaphilones from a deep-sea derived fungus Penicillium sp. SCSIO41030.

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived Penicillium sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 μM and 20 μM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aβ25-35-induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 μM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aβ25-35-induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.

Unusual immunosuppressive pyridine-containing bisnor- (c23), tetranor- (c21) and pentanor- (c20) sesterterpenoids from Tibetan Leucosceptrum canum.

An unusual pyridine-containing sesterterpenoid, leucosceptrodine (1), and five new nor-leucosceptrane sesterterpenoids, including bisnor- (C23, 2), tetranor- (C21, 3) and pentanor- (C20, 4-6) skeletons, were isolated from the leaves of Tibetan Leucosceptrum canum. Their structures including their absolute configurations were determined by extensive spectroscopic analyses and quantum chemical calculations. A single crystal of one epimer (5) was crystallized from a pair of inseparable epimers, and its structure including its absolute configuration was determined by X-ray crystallographic analysis. The immunosuppressive activities of compounds 1-4 with different potencies were evaluated by inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

A novel off-line multi-dimensional high-speed countercurrent chromatography strategy for preparative separation of bioactive neolignan isomers from Piper betle. L

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate–methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate–methanol–water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1′S)-1′-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1–6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae)

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as “Jin Guo Lan”. Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1–8), and 18 known diterpenoids (9–26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 μM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 μM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 that were increased by LPS stimulation.

Undescribed indole lactones from Alstonia scholaris protecting hepatic cell damage

Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F–K (1−6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C5→C20-olide, while compound 3 possesses unique degraded C18 and C19. The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-ĸB, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be significantly downregulated by compounds 1−6, which showed potent anti-inflammatory bioactivity.

Guided discovery of hepatoprotective polyhydroxy cembrane-type diterpenoids from the gum resin of Boswellia carterii by MS/MS molecular networking

Seven previously undescribed polyhydroxy cembrane-type diterpenoids, olibanols A-G (1–7) were obtained from the gum resin of Boswellia carterii by means of MS/MS molecular networking. Compound 2 possessed four hydroxy groups, 1, 3, 4, 5, and 6 had three hydroxy groups, 7 with one hydroxy group, among which 1 and 4 were a pair of epimers with double bond at C-3 and hydroxy at C-8. Structures of these previously undescribed compounds were determined by NMR analysis and ECD calculations. All the polyhydroxy cembrane-type diterpenoids obtained were assayed for their hepatoprotective effects against the anti-tuberculosis drug-induced hepatic damage to the HRZ-induced HepG2 cells. As results indicated, compounds 3, 4, and 6 showed significant hepatoprotective effects against the hepatic damage via the Nrf2 signal pathway, which could be developed as potential hepatoprotective agents against the anti-tuberculosis drug-induced hepatic damage.

Hosimosines A-E, structurally diverse cytisine derivatives from the seeds of Ormosia hosiei Hemsl. et Wils

Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O. hosiei have been used as traditional Chinese medicine to treat hernia, abdominal pain, blood stasis and amenorrhea. Cytisine-like and angustifoline type alkaloids were main components identified from this plant. In our research on the bioactive alkaloids from the promising Chinese medicinal plants, four new angustifoline type alkaloids (1–4) and a new cytisine-like alkaloid (5), named hosimosine A-E, together with 13 known analogues (6–18) were isolated from the seeds of O. hosiei. Their structures were elucidated by the extensive spectroscopic methods, especially the interpretation of NMR spectra and specific rotations, along with the methods of NMR and ECD calculation. Compounds 1–4 were identified as two pairs of epimers, whose relative configurations were deduced from density functional theory (DFT) calculations of NMR chemical shifts and DP4+ analysis, and absolute configurations were determined by comparison of their experimental and theoretical ECD spectra. Compound 5 displayed two sets of NMR data caused by the existence of tautomeric forms. Compounds 14, 17 and 18 were determined to be enantiomers of literature compounds. Some of the isolates exhibited moderate cytotoxic effects against HepG2, A2780 and MCF-7 cells.

Pogocablenes A-O, fifteen undescribed sesquiterpenoids with structural diversity from Pogostemon cablin

Fifteen previously undescribed sesquiterpenoids (pogocablenes A-O), three first discovered natural patchoulol-type ones, coupled with fourteen known ones, were isolated from the aerial parts of Pogostemon cablin. Among them, pogocablenes A and B, a pair of C2 epimers, possessed an unusual carbon skeleton with bicyclo[4.3.1]decane core. Pogocablene C, originated from eudesmane-type sesquiterpenoid, had an unprecedented bicyclo[5.4.0]undecane scaffold with a peroxy hemiactetal moiety. Pogocablene D possessed a rare tricyclo[5.2.2.01,5]undecane carbon skeleton derived from guaiane-type sesquiterpenoid. Pogocablene E was a 4,5-seco-guaiane derivative owning a peroxy hemiactetal unit and a spirocyclic skeleton. Pogocablene M was a nor-patchoulol-type sesquiterpenoid with α,β-unsaturated ketone moiety. Their structures with absolute configuration were determined by extensive spectroscopic analysis, in combination with quantum chemical calculation. In addition, the plausible biogenetic pathways of pogocablenes A-E were proposed. Furthermore, all isolates were evaluated for anti-influenza virus and anti-inflammatory effects.