Dihydrofuran Ring Research Articles

Studies toward the tricyclic core of phomactin A. Synthesis of the reduced furanochroman subunit.

An approach to the tricyclic core of phomactin A is described via the synthesis of a reduced furanochroman model. Key elements of this study include the use of a highly functionalized 1-oxadecalone derivative as a template for the stereoselective introduction of functionality and a tandem retro aldol-epoxide opening-cyclization sequence for elaboration of the dihydrofuran ring.

Thermal reactions of 2,3-dihydrobenzofuran: Experimental results and computer modeling

The thermal reactions of 2,3-dihydrobenzofuran were studied behind reflected shock waves in a pressurized-driver single-pulse shock tube over the temperature range 1040–1270 K and overall densities of ≈3×10 −5 mol/cm 3 . One isomerization product, o -hydroxystyrene, and products resulting from unimolecular cleavage of the furan ring were obtained under shock heating. Post-shock analysis revealed the presence of the following products in order of decreasing abundance: o -hydroxystyrene, carbon monoxide, benzofuran, benzene, ketene, toluene, ethylene, ethylbenzene, styrene, methane, acetylene, and ethane. Trace quantities of allene and propyne were also observed. In addition to H-atom ejection from the dihydrofuran ring and further decomposition of the intermediates, the molecule undergoes four unimolecular reactions involving cleavage of the furan ring and one reaction where H 2 is eliminated from the dihydrofuran ring to produce benzofuran. Two of the ring cleavage reactions yield stable products and two decompositions yield unstable intermediates, which are responsible for initiating the free radical reactions in the system. The reactions that produce stable products are dihydrobenzofuran→CH 2 CO+C 6 H 6 and dihydrobenzofuran →CO+C 6 H 5 −CH 3 . The reactions that produce unstable intermediates are dihydrobenzofuran→HCO • +C 6 H 5 −CH 2 • and dihydrobenzofuran→CH 3 CO • +C 6 H 5 • . A concise reaction scheme containing 25 species and 31 elementary reactions was constructed, and computer modeling was performed including sensitivity analysis. The agreement between the experimental and the calculated yields is very good.

(R)-Spiro[(2R)-N-acetyl-2-phenyl-1,3-thiazolidine-4,3'-(3a'R,6a'S)-5',6a'-dimethyl-3a',-6a'-dihydro-3H-furo[2,3-b]furan-2-one

In the title compound, C 18 H 19 NO 4 S, the two furan rings are fused cis. The dihydrofuran ring is practically planar and the saturated furan-2-one ring is only slightly puckered. The thiazolidine ring has a twisted conformation about the C4-S1 bond. The environment around the spiro atom is nearly tetrahedral.

A novel macrodiolide synthesis using the Mn(III)-based radical cyclization of terminal alkadienes and oligomethylene di(3-oxobutanoate)s

α,α,ω,ω-Tetraphenyl-α,ω-alkadienes reacted with oligomethylene di(3-oxobutanoate)s in the presence of manganese(III) acetate at 100 °C under an argon atmosphere to give new 12 to 22-membered macrocyclic compounds which were two fused dihydrofuran rings in a one-step procedure.

Stereoselective synthesis of dihydrofurans under phase-transfer catalyzed conditions

Treatment of cyclic or acyclic α-haloenones with various carbon nucleophiles involving active methylene functions afforded the corresponding dihydrofurans in a stereoselective manner with good to high yields. This reaction system can provide a general and practical methodology for the construction of dihydrofuran rings.

Inhibition of the cytotoxicity of protein toxins by a novel plant metabolite, mansonone-D.

We have studied the effect of several structurally related mansonones on the cytotoxicity of plant and bacterial toxins in Vero and BER-40, a brefeldin A-resistant mutant of Vero cells. Mansonone-D (MD), a sesquiterpenoid ortho-naphthoquinone, inhibited the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in Vero cells to different extents. The inhibition of ricin cytotoxicity was dose dependent and reversed upon removal of the drug. Protection of ricin cytotoxicity was also observed in the presence of cycloheximide, indicating that de novo protein synthesis is not required for the protective effect. Although MD inhibited the degradation and excretion of ricin, the binding and internalization of ricin was not affected. In contrast, MD strongly reduced the specific binding of diphtheria toxin in Vero cells. Fluorescence microscopic studies show that MD treatment dramatically alters the morphology of the Golgi apparatus in Vero cells. The kinetic studies reveal that the protection of ricin cytotoxicity is the consequence of decreased toxin translocation to the cytosol in MD-treated cells. The reactive ortho-quinone moiety of MD is important for the protective effect as thespesone, a para-naphthoquinone with a heterocyclic ring structure identical to that of MD, did not inhibit the cytotoxicity of toxins. Thespone, a dehydromansonone-D, lacking two hydrogens from the heterocyclic dihydrofuran ring of MD, inhibited the cytotoxicity of ricin, but was albeit less potent than MD. Neither mansonone-E nor mansonone-H with reactive ortho-quinone moiety, but with a different heterocyclic structure, had any effect on the cytotoxicity of ricin indicating that the protective effect of MD is specifically related to the overall structure of the metabolite.

Stereoisomers of 3-(2,3-dihydrobenzofuran-2-yl)quinuclidine: preparation and muscarinic receptor affinities.

The four stereoisomers of the antimuscarinic 3-(2,3-dihydrobenzofuran-2-yl)quinuclidine have been prepared by a method involving chromatographic separation of the racemic diastereoisomers as borane complexes. The relative and absolute configurations of the stereoisomers were determined by X-ray crystallographic methods. The crystal structure of (2'R,3R)-3-(2,3-dihydrobenzofuran-2-yl)quinuclidine.HCl.H2O contains two independent molecules with different conformations of both the quinuclidine moiety and the dihydrofuran ring.

(−)-Galanthaminium Bromide

The crystal structure and absolute configuration of the title compound, C17H22NO3+.Br−, the hydrobromide salt of the alkaloid galanthamine, is reported. The tetra­hydro­azepine ring is in a chair conformation, the dihydrofuran ring in an envelope conformation and the cyclohexene ring between an envelope and a half-chair conformation. The axial hydroxyl group forms an intramolecular hydrogen bond with the O atom of the dihydrofuran ring. The N-methyl group is in an axial position while in galanthamine it is in an equatorial position.

Mass spectral study of isomeric benzoxazolinones by electron ionisation

The electron impact mass spectra of isomeric dihydrofurobenzoxazolinones, (1–3), hydroxy (2-methyl-2-propenyl)benzoxazolinones (4–5) and (2-methyl-2-propenyloxy)benzoxazolinones (6–7) are studied. The mass spectra of 1–3 show differences in the relative abundance of an ion at m/z 163. A mechanism involving the heteroatom of the benzoxazolinone ring which is para to the oxygen of the dihydrofuran ring has been proposed to explain the results. The mass spectra and collision-induced dissociation spectra of molecular ions of 4 and 5 are similar to those of 1 and 2, respectively, suggesting the rearrangement of 4 and 5 to 1 and 2, respectively, in the source of the mass spectrometer. The fragmentation of 6 and 7 supports the proposition of dihydrofuran ring opening in 1–3. The fragmentation of 6 and 7 is different in comparison to 4 and 5, suggesting that 6 and 7 do not rearrange to 4 and 5, respectively, either before or after ionisation.

Behavioural and neurophysiological responses of Spodoptera littoralis to azadirachtin and a range of synthetic analogues

AbstractThe antifeedant activity of azadirachtin and 56 azadirachtin analogues, including 22, 23‐dihydroazadirachtin, against larvae of Spodoptera littoralis was investigated using behavioural and electrophysiological bioassays. None of the analogues was as active as azadirachtin, although many showed significant antifeedant activity at high concentrations. The majority of the analogues stimulated a dose‐dependent response from a neurone in the medial styloconic maxillary sensilla which correlated with the behavioural activity. Methylation of the hydroxy substitutions on the azadirachtin molecule usually resulted in a decrease in antifeedant activity, as did the addition of bulky groups to the dihydrofuran ring.

Constituents of Domestic Citrus Plants. Part XXIII. Citbismine-A, -B and -C, New Binary Acridone Alkaloids from Citrus Plants.

Three novel dimeric acridone alkaloids named citbismine-A (1), -B (3) and -C (5) have been isolated from the roots of Marsh grapefruit (Citrus paradisi) and Hirado-buntan (C. grandis). The structure of citbismine-A was elucidated as 1 by spectroscopic studies and single crystal X-ray analysis. Structure assignments of citbismine-B (3) and -C (5) were based on spectroscopic data including two dimensional (2D)-NMR (correlation spectroscopy (COSY) and heteronuclear multiple bond correlation (HMBC)) experiments. The common structural characteristic is the presence of a C-C bond between the aromatic ring and the dihydrofuran ring of each acridone nucleus.

Structure of Furobinordentatin, a Novel Bicoumarin from Citrus yuko.

The structure of furobinordentatin, isolated from the root of Citrus yuko (Rutaceae), has been elucidated by spectroscopic studies and a single crystal X-ray analysis as 1. Furobinordentatin is a novel type of bicoumarin composed of two nordentatin (2) units linked with the forming of a dihydrofuran ring.

Transformations of dubinidine methiodide and related compounds in an alkaline medium and on pyrolysis

The interaction of dubinidine methiodide with dilute aqueous ammonia solution and with pyridine at room temperature has been studied. In the first case the dihydrofuran ring opens, and in the second case dequaternization takes place. The dynamics of the latter process have been investigated with the aid of PMR spectroscopy, the pyrolytic transformation of dubinidine and dubinine methiodides has been studied by electron-impact mass spectrometry.

ChemInform Abstract: Highly Periselective (2,3)Wittig Rearrangements on Dihydrofuran and Dihydropyran Rings.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Photoinduced molecular transformations. Part 127. A new [2 + 2] photoaddition of 2-amino-1,4-naphthoquinone with vinylarenes and the synthesis of 2,3-dihydronaphtho[1,2-b]furan-4,5-diones and 2,3-dihydronaphtho[2,3-b]furan-4,9-diones by β-scission of alkoxyl radicals generated from the resulting photoadducts

Irradiation of 2-amino-1,4-naphthoquinone and excess of vinylarenes such as styrene, its para-substituted derivatives, 2-vinylpyridine and 4-vinylpyridine in benzene with a Pyrex-filtered light at room temperature under nitrogen gave 1-aryl-1,2,2a,8b-tetrahydro-8b-hydroxycyclobuta[a]naphthalene-3,4-diones as a single product in 23–63% yields, respectively. These cyclobutanols arise from an unprecedented stereo- and regio-selective [2 + 2] photoaddition of an excited enol form of 2-amino-1,4-naphthoquinone with the vinylarenes.Irradiation of these cyclobutanols in benzene containing excess of mercury(II) oxide and iodine with Pyrex-filtered light then gave 2-aryl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones and/or 2-aryl-2,3-dihydronaphtho[2,3-b]furan-4,9-diones (31–73% yields) arising from a regioselective β-scission of the alkoxyl radicals, followed by intramolecular cyclization of the resulting radical intermediates. The substituent at the para position of the 1-phenyl group was found to control the ratio of the two types of products: a methoxy group directs the formation of the 4,5-dione exclusively, while the p-cyano group directs the formation of the 4,9-dione exclusively. This considerable dependence of the products on the substituents suggests that at least some part of the formation of the dihydrofuran ring of the 4,5 and/or 4,9-diones takes place from the ionic intermediates arising owing to β-scission. 2,3-Dihydronaphtho[1,2-b]furan-4,5-dione was found to isomerize to 2,3-dihydro[2,3-b]furan-4,9-dione on silica gel.

Structure‐odour correlation, part XV1: Macrocyclic spiro ethers

AbstractFrom cyclooctanone (1) and cyclododecanone (2) the spiro ethers 18–23 were prepared via the yne‐diols 6–11 and the ene‐diols 12–17. Hydrogenation of 21–23 leads to the spiro tetrahydrofurans 24–26.Olfactive evaluation showed that the odour of 18 (camphor, fresh, green) is very similar to that of the unsubstituted analogue B (R1, R2 = H). This can be explained by a similar steric situation of the osmophoric dihydrofuran ring in both these compounds. Increasing substitution at C‐2 (18 → 19 → 20) diminishes the camphoraceous sensation stepwise with increasing herbaceous notes. The macrocyclic spiro ethers 21–23 exhibit interesting woody fragrances with different undertones. Particularly, 22 is most pleasant with some powdery, balsamic and musk notes. The saturated spiro ethers 24–26 smell similar but very weak.

Prehispanolone, a novel platelet activating factor receptor antagonist from Leonurus heterophyllus.

1. Using an in vitro radioligand binding assay for the platelet activating factor (PAF) receptor, we have identified a novel, specific PAF antagonist, prehispanolone, from a Chinese medicinal herb Leonurus heterophyllus. 2. The presence of sodium ions inhibited specific [3H]-PAF binding to rabbit platelet membrane with an IC50 of 5.2 mM, decreased the inhibitory potency of PAF but increased the inhibitory potency of prehispanolone. 3. Prehispanolone and several of its derivatives inhibited the binding of [3H]-PAF to rabbit platelets with potencies closely resembling that of inhibition of PAF-induced aggregation. 4. The integrity of the tetrahydrofuran ring of prehispanolone is critical for its interaction with the PAF receptor. 5. By hydrogenating the dihydrofuran ring and replacing the keto group of prehispanolone with a hydroxyl group, we obtained a compound, LC5507, that is more stable and more active than prehispanolone as a PAF receptor antagonist.

Structure determination of a diuretic-glutathione conjugate by mass and n.m.r. spectrometry

1. A glutathione (GSH) conjugate of the uricosuric diuretic DBCA 6,7-dichloro-5(N,N-dimethylsulphamoyl)-2,3-dihydrobenzofuran-2-car boxylic acid, formed enzymically in rat liver 100,000g supernatant fortified with GSH, was purified by t.l.c. and h.p.l.c. 2. According to mass spectrometry the composition of the GSH-conjugate corresponded to C21H29N4O11S2Cl2. 1H- and 13C-n.m.r. studies gave the structure of the conjugate as 2-glutathionyl-3-[3,4-dichloro-5-(N,N-dimethyl sulphamoyl)2-hydroxyphenyl]-propionic acid, which indicates that GSH was bound to the chiral centre carbon and caused scission of the C-O bond in the dihydrofuran ring.

2,3-Dihydrobenzofuran analogs of hallucinogenic phenethylamines

Two 2,3-dihydrobenzofuran analogues of hallucinogenic amphetamines were prepared and evaluated for activity in the two-lever drug-discrimination paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg) and for the ability to displace [125I]-(R)-DOI [( 125I]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) from rat cortical homogenate 5-HT2 receptors. The compounds, 1-(5-methoxy-2,3-dihydrobenzofuran-4-yl)-2-aminopropane (6a) and its 7-brominated analogue 6b, possessed activity comparable to their conformationally flexible counterparts 1-(2,5-dimethoxyphenyl)-2-aminopropane (3) and its 4-bromo derivative DOB (5), respectively. The results suggest that the dihydrofuran ring in 6a and 6b models the active conformation of the 5-methoxy groups in 3 and 5. Free energy of binding, derived from radioligand displacement KA values, indicated that addition of the bromine in either series contributes 2.4-3.2 kcal/mol of binding energy. On the basis of surface area of the bromine atom, this value is 2-3 times higher than would be expected on the basis of hydrophobic binding. Thus, hydrophobicity of the para substituent alone cannot account for the dramatic enhancement of hallucinogenic activity. Although this substituent may play a minor role in orienting the conformation of the 5-methoxy group in derivatives such as 4 and 5, there appears to be some other, as yet unknown, critical receptor interaction.

New Coumarins from Citrus Plants.

Four new coumarins, named peroxytamarin (1), cis-casegravol (5), citrusarin-A (7), and citrusarin-B (8), were isolated from root of Citrus plants and their structures were elucidated by chemical and spectrometric methods. Citrusarin-B (8), a coumarin having both a dimethylpyran ring and a dihydrofuran ring in the molecule, was also synthesized.