Tetrahydrofuran Type Research Articles

Minor Lignans with Inhibitory Activity against LPS-induced NO Production from Schisandra chinensis.

Phytochemical investigation into the fruits of Schisandra chinensis led to the isolation of seven new minor lignans, schisanchignans A-G (1-7), including one benzofuran type (1), three aryltetralin type (2-4) and three tetrahydrofuran type (5-7). Their structures were established by comprehensive spectroscopic analyses, and the absolute configurations were determined by electronic circular dichroism technique including quantum chemical calculation method. Of note, this is the first report of nor-benzofuran and aryltetralin types of lignans from S. chinensis. Compounds 1, 3 and 4 exhibited mild inhibitory activity against the lipopolysaccharide-induced production of nitric oxide in murine RAW264.7 cells.

Lignan constituents with α-amylase and α-glucosidase inhibitory activities from the fruits of Viburnum urceolatum

Eleven previously undescribed lignan constituents, including five 8-O-4′ type neolignans, viburnurcosides A–E (1–5), three benzofuran type neolignans, viburnurcosides F–H (6–8), and three tetrahydrofuran type lignans, viburnurcosides I–K (9–11), were isolated from the fruits of Viburnum urceolatum. The structures of all isolates were elucidated by an extensive analysis of the NMR and HRESIMS data. The absolute configurations of these compounds were determined by quantum-chemical electronic circular dichroism calculation and comparison. The sugar units of viburnurcosides A–K were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of monosaccharides. The in vitro enzyme inhibition assay exhibited that viburnurcoside J (10) had the most potent inhibitory activity against α-amylase and α-glucosidase with the IC50 values of 19.75 and 9.14 μM, respectively, which were stronger than those of the positive control acarbose (37.31 and 26.75 μM, respectively). The potential binding modes of viburnurcoside J (10) with α-amylase and α-glucosidase were also analyzed by molecular modeling.

Structural Features of Cork Dioxane Lignin from Quercus suber L.

The dioxane lignin was isolated from extractives- and suberin-free cork (Quercus suber L.) by a modified acidolytic procedure and submitted to structural analysis by permanganate oxidation, analytical pyrolysis coupled with gas chromatography and mass spectrometry (Py-GC-MS), liquid- and solid-state nuclear magnetic resonance (NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The molecular weight (Mw = 2500 Da) was assessed by size exclusion chromatography (SEC). The results obtained show that the cork lignin is of syringyl (S)/guaiacyl (G) type with a small proportion of p-hydroxyphenyl (H) units (S:G:H molar ratio of 23:72:5). Among a dozen detected lignin structures, those linked by ether bonds, such as β-O-4' (38 mol %) and 4-O-5' (5 mol %), were the most abundant. The frequency of occurrence of β-5', β-β', 5-5', tetrahydrofuran type, and structures arising from the condensation with concomitant procyanidins was assessed. Ferulates were the only cinnamic structure detected in the cork dioxane lignin.

A New Tetrahydrofuran Lignan from Premna serratifolia Wood

Phytochemical investigation of the CHCl3 extract of Premna serratifolia (syn: P. integrifolia) wood collected in Myanmar led to the isolation of a new tetrahydrofuran type lignan, 7,9-dihydroxydolichanthin B (1), together with two known triterpenoids, oleanonic acid (2) and (2a, 3α)-dihydroxyolean-12-en-28-oic acid (3). The structure of the new compound was determined using various spectroscopic techniques, mainly 1D- and 2D-NMR, HRESIMS, IR, and optical rotation, and by comparisons with the reported literatures. Compounds 1-3 had anti-melanin deposition activities against IBMX and α-MSH induced B16-F10 mouse melanoma cell line with IC50 values of 18.4, 17.7 and 11.2 μM, respectively. However, 2 exhibited cytotoxicity at concentrations above 50 μM.

Abstract 4846: Chemotherapeutic and chemomodulatory effects of naturally occurring tetrahydrofuran type terpenoid

Abstract Naturally occurring terpenoid compounds are diverse active constituent in several plants and known of their potential anticancer activities. Camptothecin (CPT) is a topoisomerase inhibitor agent with well documented anti-neoplastic activity against several types of tumors. The purpose of this study is to investigate the potential chemotherapeutic effects of some terpenoid compounds isolated from Salvia africana lutea, Stachys aegyptiaca, Tanacetum sinaicum. Terpenoid compounds with promising anticancer profile has been further investigated for potential chemomodulatory effects to CPT against different tumor cell types. Cytotoxicity of the isolated terpenoids were assessed against human breast adenocarcinoma (MCF7), human colorectal cancer (HCT116 and LS174T) and human hepatocellular carcinoma (HepG2) cells using sulpharhodamine-B assay after cell exposure for 72 h. Cytotoxic parameters (IC50 and R-fraction) were calculated from cell viability after fitting to Emax mathematical model. The tetrahydrofuran type terpenoid, (R,E)-6-hydroxy-6-methyl-2-((2S,5R)-methyl-5-vinyltetrahydrofuran-2-yl)hept-4-en-3-one (TSS-7), isolated from Tanacetum sinaicum showed considerable cytotoxicity with IC50 ranging from 49 to 70 μM in all tested cell lines. On the other hand, IC50 of CPT ranged from 0.13 to 1.5 μM in the same cell lines under investigation. Combination index analysis (CI-value) for TSS-7 with CPT showed synergistic relationship in MCF7, HCT116 and HepG2 (CI-values were 0.17, 0.17 and 0.39 respectively). However, the same combination of TSS-7 and CPT against LS174T cells showed antagonistic relationship (CI-value of 1.2). Further investigation for apoptosis/necrosis assessment using annexin-V/PI staining was undertaken for single and combination treatment of CPT and TSS-7. In HCT116 cells, TSS-7 combination with CPT significantly increased apoptotic and necrotic cells compared to CPT treatment alone. However, in LS174T cells, TSS-7 combination with CPT significantly decreased apoptotic and necrotic cells compared to CPT treatment alone. Cell cycle analysis using DNA cytometry showed strong G2/M arrest induced by CPT treatment. Yet, TSS-7 increased cell population in S-phase and to a lesser extend in G2/M-phase which might be the reason for temporal synergism/antagonism of TSS-7 and CPT in different cell lines. In conclusion, TSS-7 could be considered promising anticancer chemomodulatory terpenoid compound which requires further molecular investigations to elucidate its sub-cellular molecular target. Citation Format: Eman M. Atiya, Fahad A. Al-Abbasi, Mohamed-Elamir F. Hegazy, Ali M. El-Halawany, Ahmed M. Al-Abd. Chemotherapeutic and chemomodulatory effects of naturally occurring tetrahydrofuran type terpenoid. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4846.

Kinetic and mechanistic insight into Lewis base and acid-mediated phenylselenoetherification of 2,6-dimethyl-hept-5-en-2-ol

Mechanistic and kinetic aspects, as well as quantum chemical calculations, for the formation of a tetrahydrofurane ring by cyclization of the highly substituted alcohol–2,6-dimethyl-hept-5-en-2-ol with phenylselenohalides (PhSeCl and PhSeBr), in the presence of various Lewis bases (piperidine, triethylamine, pyridine and quinoline) and Lewis acids (CoCl2, SnCl2) as additives were studied. The substituted tetrahydrofuran ring is common motif in many natural products, especially in bioactive marine macrolides. Due to the presence of additives in reactions, the high regioselectivity was achieved, and the tetrahydrofuran type of ether in all studied reactions was obtained in excess in regard to the six-membered cyclic ether. In addition, kinetic aspects of reactions mediated by Lewis bases were studied by UV–Vis spectroscopy (in THF, at 288 K), as reactions of pseudo-first-order. Obtained values for rate constants proved catalytic role of additives and indicated that the reaction rate depends on pKa values of used base as well as on their ability for formation of hydrogen bond with OH–alcohols group.

Biological activities of lignoids from Amazon Myristicaceae species: Virola michelii, V. mollissima, V. pavonis and Iryanthera juruensis

This work revisits the fruits of Iryanthera juruensis and Virola pavonis and the leaves from V. michelii, as well as describing a study of the fruits of V. mollissima. In I. juruensis aryltetraline neolignan (1) and tetrahydrofuran neolignan (2), were found while from V. pavonis neolignans of benzofuran type (6-9), the tetrahydrofuran type (2, 11-13, 17) and the biphenyl type (10), in addition to diastereoisomers of the 8.O.4'-oxyneolignan type (14 and 15) and others were isolated. The V. mollissima accumulates the aryltetralone neolignan 4 and its seco derivative (5). The lignoids 1 and 2 obtained from I. juruensis arils possess antileishmanial activity against the promastigote form of Leishmania amazonensis.

Facile pyridine-catalyzed phenylselenoetherification of alkenols

An innovative route for intramolecular cyclization of alkenols has been delineated through a ring closing reaction of suitably alkenols functionalized cyclic ethers tetrahydropyran or tetrahydrofuran type by reaction with phenylselenyl halides, in good yield. Proper choice of some Δ 4- and Δ 5-alkenols and pyridine as catalyst enables fast and facile cyclization. Catalytic amount of pyridine increased the yield, but in the presence of equimolar amount of pyridine, formation of corresponding cyclic ethers were quantitative and reaction were achieved instantaneously under extremely mild experimental conditions. It is possible that aromatic–aromatic ring stacking provides such role of pyridine. The effect of the steric hindrance in the starting alkenols, and halide ion of the selenenylating reagent is not significant, all halides generally giving equal results, and primary, secondary, tertiary and more substituted alkenols also giving quantitative yields.

An Improved Phenylselenoetherification of Pent-4-en-1-ol

The procedure employs phenylselenyl chloride or bromide, pent-4-en-1-ol, and additives, like pyridine and silver(I) salts, to generate the cyclic ether of tetrahydrofuran type in high yields. A catalytic amount of additive leads to higher yields, but equimolar amounts achieved almost quantitative yields under extremely mild experimental conditions. The effect of the halide ion of the selenylating reagent is not significant.

A General Approach to the Asymmetric Synthesis of Lignans: (-)-Methyl Piperitol, (-)-Sesamin, (-)-Aschantin, (+)-Yatein, (+)-Dihydroclusin, (+)-Burseran, and (-)-Isostegane

A highly efficient, diastereo- and enantioselective route was developed to access a great variety of lignans. The asymmetric synthesis of the 2,3-disubstituted γ-butyrolactones 9a-c could be improved in the case of aldol reactions by employing 2.2 equivalents of LiCl as an additive to provide, after purification, highly diastereo- and enantioenriched starting materials for the synthesis of the furofuran lignans (-)-methyl piperitol, (-)-sesamin, and (-)-aschantin. Furthermore, the γ-butyrolactone 15 was converted into dibenzylbutyrolactone lignan (+)-yatein, the dibenzylbutandiol type (+)-dihydroclusin, the tetrahydrofuran type (+)-burseran, and the dibenzocyclooctadiene type (-)-isostegane.

First stereoselective synthesis of (+)-magnostellin C, a tetrahydrofuran type of lignan bearing a chiral secondary benzyl alcohol.

(+)-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.

Preparation of alkali metal-graphite intercalation compounds in tetrahydrofuran type of solvents

Preparation of alkali metal-graphite intercalation compounds in tetrahydrofuran type of solvents

Intramolecular Cyclization of Some Unsaturated Alcohols by Means of Thallium Triacetate

AbstractReactions of some primary and secondary Δ4‐, Δ5‐ and Δ6‐alkenols with thallium triacetate (TTA) in benzene, acetic acid and chloroform as solvent have been investigated. When terminally unsubstituted Δ4‐alkenols, such as 4‐penten‐1‐ol (5a) and 5‐hexen‐2‐ol (5b), are treated with TTA in benzene, β‐acetoxylated tetrahydrofurans 8a and 8b are obtained. However, when the reaction is carried in acetic acid the products are both regioisomers, i.e. five‐ and six‐membered cyclic ethers (8a, 8b, 7a and 7b). 4‐Methyl‐4‐penten‐1‐ol (5c) is converted in benzene into a mixture of products (8c and 7c) in which the tetrahydropyran derivative 7c is predominant, and in acetic acid it is the sole cyclization product. Terminally dialkylated alkenols, such as 5‐methyl‐4‐hexen‐1‐ol (1b) and 6‐methyl‐5‐hepten‐2‐ol (1c), are converted into β‐acetoxylated (4b and 4c) and unsaturated cyclic ethers (9a and 9b), in both cases of the tetrahydrofuran type. 5‐Hexen‐1‐ol (10) and 6‐hepten‐1‐ol (11) cyclize to the corresponding six‐ (13) and seven‐membered cyclic ether (14), respectively. Organothallium intermediates have been isolated and identified in the cases of alcohols 5a, 5c and 10, proving that the TTA addition to the double bond has originally obeyed the Markovnikov rule.