lignans and tetrahydrofuran

Different strategies for the racemic or enantiospecific total syntheses of plant and mammalian 3,4-dibenzyltetrahydrofuran lignans are reviewed and compared. The multi-step approaches have various key step strategies: Diels-Alder reactions, Stobbe condensations, Michael additions, alkylations, nitrile oxide cycloadditions, radical cyclisations, dianion and oxidative couplings.

Topics: Furans; Lignans; Molecular Structure; Stereoisomerism

Lignans are widely existed in natural world with a variety of structures and bioactivities, including anti-tumor, antiinflammatory, anti-viral and hepatoprotective properties. Along with the development of new techniques in phytochemistry and application of advanced drug screening methods, a variety of lignans have been identified and their bioactivities revealed. In this review, we summarized the activities of six different types of lignans, including arylnaphthalene, dibenzylbutyrolactone, tetrahydrofuran, dibenzylbutane, dibenzocyclooctadiene and neolignan, in order to provide an updated overview of this research field.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antiviral Agents; Cyclooctanes; Furans; Humans; Lignans; Molecular Structure; Plants, Medicinal

One novel tri-substituted tetrahydropyran type 8,7'-neolignan and its enantiomer with higher enantiomeric excess were synthesized from all

Topics: Lactuca; Lignans; Lolium; Stereoisomerism

Chemical scaffolds of natural products have historically been sources of inspiration for the development of novel molecules of biological relevance, including hit and lead compounds. To identify new compounds active against Trypanosoma cruzi, we designed and synthesized 46 synthetic derivatives based on the structure of two classes of natural products: tetrahydrofuran lignans (Series 1) and oxazole alkaloids (Series 2). Compounds were screened in vitro using a cellular model of T. cruzi infection. In the first series of compounds, 11 derivatives of hit compound 5 (EC

Topics: Alkaloids; Biological Products; Dose-Response Relationship, Drug; Drug Design; Furans; Humans; Lignans; Molecular Structure; Oxazoles; Parasitic Sensitivity Tests; Structure-Activity Relationship; Trypanocidal Agents; Trypanosoma cruzi

Four previously undescribed tetrahydrofuran lignans, named anorisols A-D (1-4) and fourteen known compounds (5-18) were isolated from the roots, stems, leaves and twigs of Anogeissus rivularis. The chemical structures were elucidated on the basis of their spectroscopic data and by comparison with the literature data. The absolute configurations of 1-4 were established by comparison of the experimental ECD spectra with the calculated ECD spectra. Some isolated compounds were evaluated for their cytotoxic activity as well as anti-HIV-1 activity employing reverse transcriptase (RT) and syncytium reduction assays using the

Topics: Anti-HIV Agents; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Combretaceae; Furans; Humans; Lignans; Molecular Structure; Phytochemicals; Plant Leaves; Plant Roots; Plant Stems; Reverse Transcriptase Inhibitors; Thailand

Topics: Animals; Anti-Inflammatory Agents; China; Fruit; Furans; Lignans; Mice; Molecular Structure; Nitric Oxide; Phytochemicals; RAW 264.7 Cells; Terminalia

Tumors adapt to hypoxia by regulating angiogenesis, metastatic potential, and metabolism. These adaptations mediated by hypoxia-inducible factor 1 (HIF-1) make tumors more aggressive and resistant to chemotherapy and radiation. Therefore, HIF-1 is a validated therapeutic target for cancer. In order to develop new HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural product manassantin A, we synthesized and evaluated manassantin A analogues with modifications in the tetrahydrofuran core region of manassantin A. Our structure-activity relationship study indicated that the α,α'-

Topics: ErbB Receptors; Furans; HEK293 Cells; Humans; Lignans; Protein Kinase Inhibitors

Isoxazole analogues derived from the neolignans veraguensin, grandisin, and machilin G were previously synthesized with different substitution patterns through the bioisosterism strategy. These compounds were tested on intracellular amastigotes of Leishmania (Leishmania) amazonensis; the derivatives proved to be active against intracellular amastigotes, with IC

Topics: Animals; Antiprotozoal Agents; Drug Design; Female; Furans; Inhibitory Concentration 50; Isoxazoles; Leishmania; Life Cycle Stages; Lignans; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Nitric Oxide; Structure-Activity Relationship; Triazoles

Myristica fragrans Houtt., the source of very important spice 'nutmeg' used world over is native to India, Indonesia, Sri Lanka, South Africa and Southeast Asia. Phytochemical investigation of M. fragrans stem bark led to the isolation of bis-aryl dimethyl tetrahydrofuran lignans, such as grandisin [(7S,8S,7'S,8'S)-3,3',4,4',5,5'-hexamethoxy-7,7',8,8'-lignan] and (7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7,7',8,8'-lignan along with important lignans and neolignans, licarinA, licarin B, odoratisol A, (2S, 3R)-7-methoxy-3-methyl-5-((E)-prop-1-enyl)-2-(5-methoxy,3,4-methylenedioxyphenyl)-2,3-dihydrobenzofuran, elemicin, fragransin B

Topics: Anisoles; Benzofurans; Dioxoles; Furans; India; Indonesia; Lignans; Molecular Structure; Myristica; Phytochemicals; Plant Bark; Spectrum Analysis; Sri Lanka

EtOAc extract from the leaves of Terminalia citrina collected in Bangladesh were separated, and seven previously undescribed α-keto tetrahydrofuran lignan glucosides (terminalosides Q to W) were isolated and characterized. NOESY analysis of

Topics: Antineoplastic Agents, Phytogenic; Bangladesh; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Estradiol; Furans; Glucosides; Humans; Lignans; Molecular Structure; Plant Leaves; Plants, Medicinal; Structure-Activity Relationship; Tumor Cells, Cultured

A very short three-step approach to trans,trans,trans-2,5-diaryl-3,4-dimethyltetrahydrofuran lignans is reported. The carbon skeleton is assembled in a single step based on an unprecedented tandem reaction consisting of 1,2-addition of aryllithium reagents to α,β-unsaturated aldehydes, ruthenium-catalyzed redox isomerization of the resulting alkoxides to enolates and their dimerization triggered by single electron oxidation. The resulting 2,3-dialkyl-1,4-diketones form with moderate to good d/l-diastereoselectivity and are transformed to the target tetrahydrofuran lignans by reduction and diastereoselective cycloetherification.

Topics: Aldehydes; Biomimetics; Catalysis; Chemistry Techniques, Synthetic; Crystallography, X-Ray; Cyclization; Furans; Isomerism; Lignans; Models, Molecular; Oxidation-Reduction; Oxidative Coupling; Ruthenium

Two new tetrahydrofuran lignans, taungtangyiols A (1) and B (2), and eight known furofuran lignans (3-10), were isolated from the chloroform extract of Premna integrifolia wood collected in Myanmar. Their structures were elucidated by extensive spectroscopic techniques. The X-ray crystal structure of 1 clearly indicated its relative configuration. Taungtangyiols A (1) and B (2) inhibited the deposition of melanin in B16F10 mouse melanoma cells, with IC

Topics: Animals; Cell Line, Tumor; Furans; Lamiaceae; Lignans; Melanins; Melanoma, Experimental; Mice; Molecular Structure; Myanmar; Wood

An unusual tetrahydrofuran lignin, zanthplanispine (1), together with 14 known lignans (2 - 15) were isolated from the AcOEt-soluble fraction from the MeOH extract of Z. planispinum roots. The structures of 1 was elucidated on the basis of 1D- and 2D-NMR experiments as well as HR-ESI-MS analysis. The known compounds were identified by the comparison of their NMR data with previously reported in the literatures. Bioassay showed that compounds 1 - 4 could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. In particular, compound 1 showed significant inhibitory activity with an IC

Topics: Animals; Anti-Inflammatory Agents; Furans; Inhibitory Concentration 50; Lignans; Mice; Nitric Oxide; Plant Extracts; Plant Roots; RAW 264.7 Cells; Zanthoxylum

A phytochemical investigation of the EtOH extract from the aerial parts of Viburnum betulifolium Batal. afforded four new tetrahydrofuran lignans, betulifolium A-D (1, 2, 4, and 5), together with two known compounds vibsanol-9'-al (3) and sarcomeginal (6). This paper deals with the isolation and structure elucidation of the new compounds on the basis of spectroscopic methods, including 1D NMR, 2D NMR analyses and HR-ESI-MS data.

Topics: Benzofurans; Diterpenes; Drugs, Chinese Herbal; Furans; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Viburnum

Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.

Topics: Animals; Antiprotozoal Agents; Furans; Humans; Leishmania; Leishmaniasis; Lignans; Macrophages; Nitric Oxide; Structure-Activity Relationship

Acid-catalyzed degradation of lignin in toluene containing methanol selectively yields C6-C2 lignin monomers and releases lignin oligomers, a potential raw feedstock for epoxy resins. We herein characterize the structures of the lignin oligomers by focusing on the changes in the interunit linkage types during solvolysis. The oligomeric lignin products were analyzed via thioacidolysis and 2D-HSQC-NMR. The results show that lignin oligomers ranging from monomers to tetramers are released through considerable cleavage of the β-O-4 linkages. The lignin oligomers from Cryptomeria japonica (softwood) mainly comprise β-5, β-1, and tetrahydrofuran β-β linkages, whereas Eucalyptus globulus (hardwood) yields oligomers rich in β-1 and syringaresinol β-β linkages. Both wood samples exhibit selective release of β-β dimers and a relative decrease in 5-5 and 4-O-5 bonds during solvolysis. The method presented for the separation of lignin oligomers without β-O-4 linkages and with linkages unique to each wood species will be useful for the production of lignin-based materials.

Topics: Cryptomeria; Eucalyptus; Furans; Gas Chromatography-Mass Spectrometry; Lignans; Lignin; Magnetic Resonance Spectroscopy; Molecular Structure; Wood

Lignan natural products comprise a broad spectrum of biologically active secondary metabolites. Their structural diversity belies a common biosynthesis, which involves regio- and chemoselective oxidative coupling of propenyl phenols. Attempts to replicate this oxidative coupling have revealed significant challenges for controlling selectivity, and these challenges have thus far prevented the development of a unified biomimetic route to compounds of the lignan family. A practical solution is presented that hinges on oxidative ring opening of a diarylcyclobutane to intercept a putative biosynthetic intermediate. The effectiveness of this approach is demonstrated by the first total synthesis of tanegool in 4 steps starting from ferulic acid, as well as a concise synthesis of the prototypical furanolignan pinoresinol.

Topics: Biomimetics; Coumaric Acids; Furans; Lignans; Oxidation-Reduction; Phenols

(-)-Talaumidin (1), a 2,5-biaryl-3,4-dimethyltetrahydrofuran lignan isolated from Aristolochia arcuata Masters, shows significant neurite-outgrowth promotion and neuroprotection in primary cultured rat cortical neurons and in NGF-differentiated PC12 cells. The four stereogenic centers on the tetrahydrofuran moiety in 1 result in the presence of seven diastereomers except for their enantiomers. In order to investigate the stereochemistry-activity relationships of the stereoisomers, the systematic synthesis of all stereoisomers of 1 was accomplished by employing Evans aldol, diastereoselective hydroboration, reductive deoxygenation, and Mitsunobu reactions as key steps. The ability of all of the synthesized stereoisomers to promote neurite-outgrowth in PC12 and neuronal cells was evaluated. All stereoisomers exhibited moderate to potent neurotrophic activities in NGF-differentiated PC12 cells at 30 μM and in primary cultured rat cortical neuronal cells at 0.01 μM. In particular, 1e bearing all cis substituents resulted in the most potent neurite-outgrowth promotion.

Topics: Animals; Aristolochia; Cell Differentiation; Cell Line; Furans; Lignans; Nerve Growth Factors; Neurons; PC12 Cells; Rats; Stereoisomerism

A synthesis of natural tetrahydrofuran lignan (+)-sylvone is achieved starting from methyl allenoate in 5 steps. The synthesis begins from an enantioselective aldol reaction of methyl allenoate with 3,4-dimethoxybenzaldehyde to afford α-addition aldol adduct. Key steps for the synthesis of sylvone include an oxacyclization of the α-hydroxy allenyl adduct followed by a Michael addition of a 1,3-dithiane derivative to establish a sylvone skeleton with suitable stereoselections.

Topics: Benzaldehydes; Catalysis; Furans; Heterocyclic Compounds; Lignans; Molecular Structure; Naphthalenes; Stereoisomerism

To study the chemical constituents from the stems and leaves in Drypetes hainanensis.. The constituents were isolated and purified by various chromatography, and the structures were identified by extensive spectral analysis.. Eleven compounds were isolated and identified as syringaresinol-4-O-glycoside (1), koaburaside (2), abietin (3) syringin (4), kelampayoside A (5), 7,7'-bis-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-dihydroxymethyl-tetrahydrofuran-4-O-β-glucopyranoside (6), amentoflavone (7), 3,4,5-trimethoxyphenyl-β-D-glucopyranoside (8),1,4-di-O-methyl-myo-inositol (9), glycerol (10) and succinic acid (11).. All the compounds are isolated from this plant for the first time.

Topics: Drugs, Chinese Herbal; Furans; Glucosides; Glycosides; Lignans; Magnoliopsida; Phenylpropionates; Phytochemicals; Plant Leaves; Plant Stems; Plants, Medicinal

A new tetrahydrofuran-type lignan, episesaminone (1), was isolated from Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. Its structure was established by spectroscopic techniques (HR-MS, 1D NMR, 2D NMR, and circular dichroism). The anti-inflammatory activity in RAW 264.7 macrophages was carried out on 1 and other eight known compounds, the epimer of 1 (2) and seven known furofurans-type lignan (3-9) obtained from A. heterotropoides Fr. Schmidt var. mandshuricum. Compounds 1, 2, 3, 4, 5, 7, and 9 showed significant anti-inflammatory activity, particularly 50 μM compound 3 inhibited 69.2% NO production compared with the lipopolysaccharide group.

Topics: Algorithms; Animals; Anti-Inflammatory Agents; Asarum; Drugs, Chinese Herbal; Furans; Lignans; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; Nitric Oxide; Nuclear Magnetic Resonance, Biomolecular; Plant Roots

Five new diaryldimethylbutane lignans, saurulignans A-E (1-5), four new tetrahydrofuran lignans, saurufurins A-D (6-9), and one arylnaphthalene lignan, saurunarin (10), were isolated from Saururus chinensis, along with 18 known compounds. Lignan 5 showed significant inhibition of ADP-induced aggregation with an IC50 value of 9.8 μM and AA-induced aggregation with an IC50 value of 14.0 μM. Compound 19 showed significant activity to inhibit PAF-induced aggregation with an IC50 value of 9.1 μM. In addition, five isolated compounds could induce platelet aggregation. These results suggest that secondary metabolites in S. chinensis have bidirectional regulation on blood clotting and anticlotting effects.

Topics: Algorithms; Animals; Furans; Inhibitory Concentration 50; Lignans; Molecular Structure; Plant Roots; Platelet Aggregation; Saururaceae; Taiwan

Bioinspired total synthesis of gymnothelignan N was accomplished in 13 steps and 6.7% overall yield. The synthesis features a syn Evans aldol reaction, an intramolecular hydrogenative dehydration reaction, and a phenol oxidative dearomatization/Friedel-Crafts reaction, which provides a new plausible biosynthetic pathway for the gymnothelignans and other symbiotic members. Meanwhile, another tetrahydrofuran-type lignan beilschmin A was also synthesized.

Topics: Aldehydes; Furans; Lignans; Molecular Structure; Saururaceae; Stereoisomerism

Sesaminol triglucoside is a major lignin in sesame meal and has a methylenedioxyphenyl group and multiple functions in vivo. As a tetrahydrofurofuran type lignan, sesaminol triglucoside is metabolized to mammalian lignans. This investigation studies the effect of sesaminol triglucoside and its tetrahydrofuranoid metabolites (sesaminol, 2-episesaminol, hydroxymethyl sesaminol-tetrahydrofuran, enterolactone, and enterodiol) on gene expression in primary rat hepatocytes using a DNA microarray. Sesame lignans significantly affected the expression of xenobiotic-induced transcripts of cytochrome P450, solute carrier (SLC), and ATP-binding cassette (ABC) transporters. Changes in gene expression were generally greater in response to metabolites with methylenedioxyphenyl moieties (sesaminol triglucoside, sesaminol, and 2-episesaminol) than to the tetrahydrofuranoid metabolites (hydroxymethyl sesaminol-tetrahydrofuran, enterolactone, and enterodiol). Tetrahydrofuran lignans, such as sesaminol triglucoside, sesamin, hydroxymethyl sesaminol-tetrahydrofuran, and sesaminol changed the expression of ABC transporters.

Topics: 4-Butyrolactone; Animals; ATP-Binding Cassette Transporters; Cytochrome P-450 Enzyme System; Dioxoles; Furans; Gene Expression; Gene Expression Profiling; Glucosides; Hepatocytes; Inactivation, Metabolic; Lignans; Liver; Mammals; Plant Extracts; Rats, Sprague-Dawley; Seeds; Sesamum

One new lignan (7S,8R,7'R,8'R)-7-(3,4-methylenedioxyphenyl)-8,8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3',4'-methylenedioxyphenyl)-tetrahydrofuran (1), one new sesquiterpene 2-hydroxy-11,12-dehydrocalamenene (2), one new natural product erythro-1-(3,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane (3), and two known lignans (+)-anwulignan(erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane) (4) and ( - )-zuonin-A (5) were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated by spectroscopic methods. The cytotoxicity of compounds 1 and 2 was assayed.

Topics: Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Furans; HCT116 Cells; Humans; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Stems; Schisandra; Sesquiterpenes; Stereoisomerism

A new lignan glycoside, tianshanoside A (1), together with a known phenylpropanoid glycoside, syringin (2) and two known lignan glycosides, picraquassioside C (3), and aketrilignoside B (4), were isolated from the whole plant of Viola tianshanica Maxim. The structure of the new compound was elucidated by extensive NMR (1H, 13C, COSY, HSQC, HMBC and ROESY) and high resolution mass spectrometry analysis. The three lignans 1, 3, and 4 did not exhibit significant cytotoxicity against human gastric cancer Ags cells or HepG2 liver cancer cells. This is the first report of the isolation of a lignan skeleton from the genus Viola L.

Topics: Furans; Glycosides; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Viola

Four new tetrahydrofuranoid lignans, (-)-tanegool-7'-methyl ether ( 1), (+)-7'-methoxylariciresinol (2), sinolignan C (3), and epipinoresinol-4,4'-di- O- β- D-glucopyranoside (4), were isolated from the roots and rhizomes of SINOPODOPHYLLUM EMODI together with one known lignan (5). Their structures and stereochemistry were elucidated on the basis of spectroscopic and mass spectrometric evidence. The isolation of compounds 1- 5 represents the first report of tetrahydrofuran lignans from the genus SINOPODOPHYLLUM. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines, and compound 1 showed the most potent cytotoxicity with IC₅₀ values of 9.7 µM and 4.7 µM, respectively.

Topics: Berberidaceae; Cell Line, Tumor; Cell Survival; China; Furans; Humans; Lignans; Molecular Structure; Plant Roots; Rhizome

Fifteen new lignans, gymnothelignans A-O (1-15), bearing tetrahydrofuran with variable conformations belonging to three potentially related skeletons were isolated from Gymnotheca chinensis Decne. The structures were elucidated by means of detailed spectroscopic analysis. Absolute configurations were assigned using X-ray single-crystal diffraction and chemical transformations. Moreover, by the homology, compounds 1-11 and eupomatilones were confirmed to have uniform R-configuration at C-5. However, a synthesized congener has long been mistaken as 5-epimer of eupomatilone-6. This work provides guidance for the absolute configuration establishment of the subeupomatilone family with trans-H-4-H-5 configuration.

Topics: Benzofurans; Biological Products; Crystallography, X-Ray; Furans; Lignans; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Stereoisomerism

A new tetrahydrofuranoketone lignan (1) and two new tetrahydrofuranoketone lignan glycosides (2, 3) were isolated from the ethanol extract of the aerial part of Mananthes patentiflora. The structure elucidations of these compounds were mainly established on the basis of 1D, 2D NMR and HR-mass spectroscopic analysis. All three compounds revealed potent antioxidant activities within the concentration range tested (0.08-50.0 microM).

Topics: Acanthaceae; Antioxidants; Furans; Glycosides; Lignans; Molecular Structure; Plant Components, Aerial; Plant Extracts

We have shown that manassantin A downregulated the HIF-1alpha expression and inhibited the secretion of VEGF. We have also demonstrated that the 2,3-cis-3,4-trans-4,5-cis-configuration of the tetrahydrofuran is critical to the HIF-1 inhibition of manassantin A.

Topics: Animals; Cell Line; Furans; Hypoxia-Inducible Factor 1; Lignans; Mice; Vascular Endothelial Growth Factor A

Two new tetrahydrofuran lignans, kadlongirins A and B (1, 2), a new cadinane-type sesquiterpenoid, 2,7-dihydroxy-11,12-dehydrocalamenene (3), together with seven known lignans, grandisin, fragransin B1, vladirol F, kadsuralignan C, otobaphenol, isoanwulignan, and 4-[4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-2-methoxy-phenol, were isolated from the leaves and stems of Kadsura longipedunculata. The structures of these new compounds were elucidated by spectroscopic methods. Compound 2 exhibited weak anti-human immunodeficiency virus-1 activity with an EC50 value of 16.0 microg/ml, and therapeutic index (TI) value of 6.7.

Topics: Anti-HIV Agents; Drugs, Chinese Herbal; Furans; Humans; Kadsura; Lignans; Microbial Sensitivity Tests; Molecular Structure; Phytotherapy; Sesquiterpenes

Five tetrahydrofuran lignans and two known flavones were isolated from the aerial parts of Peperomia blanda. The structures of the isolated lignans were elucidated by interpretation of their spectroscopic data, including by gHMQC and gHMBC. The relative and absolute configurations of the isolates were determined from NOESY interactions and optical properties, respectively. Four of the lignans were diastereomeric whilst one was of mixed biosynthetic origin. All but one of the lignans exhibited high in vitro trypanocidal activity when assayed against epimastigotes of Trypanosoma cruzi strain Y.

Topics: Animals; Furans; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Peperomia; Trypanocidal Agents; Trypanosoma cruzi

Bioactivity-guided fractionation of the methanol extract of the fruits of Forsythia suspensa Vahl has led to the isolation of two new monoepoxylignans, forsythialan A (1) and B (2), together with a known tetrahydrofurofuran lignan, phillyrin (3). The structures of compounds 1 and 2 were elucidated by spectroscopic methods. The antioxidant activities of these lignans have been assessed by evaluating their protective effects against peroxynitrite-induced oxidative stress. The compounds 1 and 2 showed protective effects against renal epithelial cell injury by 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator. The relatively stronger antioxidant activities of compounds 1 and 2 may be associated with the presence of aromatic hydroxy function.

Topics: Animals; Antioxidants; Chromatography, High Pressure Liquid; Forsythia; Fruit; Furans; Glucosides; Lignans; LLC-PK1 Cells; Magnetic Resonance Spectroscopy; Molecular Structure; Molsidomine; Nitric Oxide Donors; Oxidative Stress; Peroxynitrous Acid; Plant Extracts; Swine

Four new compounds, including three secolignans (1-3) and one tetrahydrofuran lignan (4), were isolated from the petroleum ether and EtOAc fractions of Peperomia heyneana. These compounds were accompanied by eight known secolignans, one known tetrahydrofuran lignan, one known cyclohexenone, and one known amide. The structures were elucidated mainly by 1D and 2D NMR and MS experiments, and the relative configurations by NOE techniques. Five compounds were evaluated for their inhibitory activities against HIV-1 in infected C8166 cells.

Topics: Anti-HIV Agents; Drugs, Chinese Herbal; Furans; HIV-1; Humans; Lignans; Molecular Structure; Peperomia; Plants, Medicinal; T-Lymphocytes

The benzyl mesylate was employed to construct the tetrasubstituted tetrahydrofuran lignan with avoiding Friedel-Crafts type of reaction. The optically pure 7,8-trans, 7',8'-trans, 7,7'-cis, and 8,8'-cis-virgatusin stereoisomers were synthesized. The enantiomeric excess was >>99%.

Topics: Benzyl Compounds; Furans; Lignans; Mesylates; Molecular Structure; Stereoisomerism

The optically pure trisubstituted 7'-oxotetrahydrofuran lignans (-)- and (+)-magnolone ( 1) were synthesized by employing stereoselective S N1 intramolecular cyclization as a key reaction. The absolute configuration of naturally occurring (-)-magnolone was determined as (7 S,8 R,8' S).

Topics: Furans; Lignans; Magnolia; Molecular Structure; Stereoisomerism

The first highly enantioselective syntheses of tetra-substituted tetrahydrofuran lignan, (-)- and (+)-virgatusin, were achieved. Hemiacetal was stereoselectively obtained from Evans's syn-aldol product as a single isomer. This hemiacetal was converted to (-)-virgatusin via hydrogenolysis. (+)-Virgatusin was also synthesized through the same process. The enantiomeric excess of the both enantiomers was determined as more than 99% ee.

Topics: Furans; Lignans; Magnetic Resonance Spectroscopy; Spectroscopy, Fourier Transform Infrared; Stereoisomerism

Five new tetrahydrofuran lignans (1-5), accompanied by four known compounds, were isolated from the ethyl acetate extract of Peperomia dindygulensis. Structures were elucidated mainly using 1D NMR, 2D NMR, and mass spectroscopic studies. The relative configurations of 1-5 were determined by NOE correlations. Several of the compounds showed weak growth inhibitory activity against three cell lines (WI-38, VA-13, and HepG2). Compound 5 exhibited stronger MDR (multidrug resistance) reversal activity than verapamil at 2.5 microg/mL in a cellular calcein accumulation assay. Compounds 4 and 5 showed weak inhibitory activity against induction of the intercellular adhesion molecule-1 (ICAM-1) in anti-inflammatory activity experiments.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Furans; Humans; Intercellular Adhesion Molecule-1; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Peperomia; Plants, Medicinal; Tumor Cells, Cultured

The phytochemical investigation of the crude ethanol extract of the leaves of Nectandra megapotamica afforded three new (2d, 3b, and 3c) and eight known (1a-d, 2a-c, and 3a) tetrahydrofuran lignans. Regarding the in vitro trypanocidal activity, the lignan-rich fraction, at a concentration of 2.0 mg/mL, was 100% active. Compound 1a was the most active, showing an IC(50) value of 2.2 microM and lysis of 94% of the parasites at 32 microM. Compounds 1b, 1d, 2a, 2c, and 3a displayed moderate activity, while compound 1c was inactive.

Topics: Animals; Brazil; Furans; Inhibitory Concentration 50; Lauraceae; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Leaves; Plants, Medicinal; Stereoisomerism; Structure-Activity Relationship; Trypanocidal Agents; Trypanosoma cruzi

(+)-Magnostellin C, which is a tetrahydrofuran type of lignan bearing a chiral secondary benzylic hydroxy group, was stereoselectively synthesized from L-arabinose by using threo selective aldol condensation.

Topics: Dioxoles; Furans; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Plants; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism

Four new tetrahydrofuran-type sesquilignans, named bonaspectin A, bonaspectin B, bonaspectin C 4''-beta-glucoside and bonaspectin D 4''-beta-glucoside, as well as two new 8.O.4'-type sesquineolignans, named neobonaspectin A and B, were isolated from the aerial vegetative parts of Bonamia spectabilis (Convolvulaceae), together with the known compound rel-(7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7.O.7',8.8'-lignan. Their structures were established on the basis of spectral data.

Topics: Africa; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Furans; Lignans; Madagascar; Magnetic Resonance Spectroscopy; Plants, Medicinal

A tetrahydrofuran lignan as well as the known tetrahydrofuran lignan, (-)-grandisin, and five phenylpropanoid derivatives were isolated from Piper solmsianum. Their structures were determined by means of spectral analyses, including 2D NMR techniques such as NOE-DIFF and HMBC 3J(C-H).

Topics: Anthracenes; Furans; Lignans; Molecular Structure; Perylene; Phenylpropionates; Piperidines; Spectrum Analysis

Two lignans of the tetrahydrofuran type, di-O-methyltetrahydrofuroguaiacin B (1) and (+)-veraguensin (2) were isolated from fruits and leaves of Illicium floridanum Ellis (Illiciaceae). These compounds are the first genuine lignans isolated from the genus Illicium. We investigated their radical scavenging potency towards 1,1-diphenyl-2-picrylhydrazyl radical reagent and their influence on luminol enhanced chemiluminescence (CHL) induced by different stimuli in human polymorphonuclear neutrophils (PMN). Both compounds were inactive in the TLC assay for chemical radical scavenge. In the PMN assay, the symmetric lignan 1 at concentrations below 1.0 microM displayed a strong inhibition of CHL induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). At concentrations above 5 microM, 1 led to a pronounced increase of fMLP induced CHL. When CHL was stimulated with opsonized zymosan, both compounds were completely inactive. Thus, 1 must interfere selectively with a step in the signal cascade evoked by fMLP. In addition to their known PAF-receptor antagonism tetrahydrofuran lignans may thus also interfere with inflammatory responses by inhibition of free radical formation.

Topics: Cell Line; Furans; Humans; Lignans; Luminescent Measurements; Luminol; Magnoliopsida; Neutrophils

Based on the inhibition of Cu(2+)-induced LDL oxidation as marker, the major antioxidants in the fruits of Forsythia suspensa and the stems of Magnolia coco were identified. Of these bioactive tetrahydrofurofuran lignans, pinoresinol, phillygenin, and syringaresinol were more potent than probucol. Sesamin and fargesin, which do not contain phenol groups, were found much less active.

Topics: Furans; Humans; Lignans; Lipoproteins, LDL; Male; Oxidation-Reduction; Plants, Medicinal

The six (racemic or meso) isomers of 3,4-dimethyl-2,5-bis(3,4-dimethoxyphenyl)tetrahydrofuran and four corresponding desmethyl analogues were prepared and assayed as inhibitors of platelet activating factor (PAF) receptor binding to rabbit platelet plasma membranes. The inhibition by these isomers is stereodependent and varies with the gross shape of the molecules as determined by the molecular mechanics program MM2. The most potent PAF antagonist in this group of compounds is trans-2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran (L-652,731, 14) with an IC50 of 0.02 microM.

Topics: Animals; Furans; Lignans; Molecular Conformation; Plant Extracts; Platelet Activating Factor; Rabbits; Structure-Activity Relationship