Rhodium (I)-katalysierte Reaktionen der [2+4]-Cycloaddukte aus 3,4-Dimethoxyfuran und Acetylendicarbonsäure-estern

[2+4]-Cycloaddition Products of 3,4-Dimethoxyfuran with Acetylenedicarboxylates and Their Transformations under the Influence of Rhodium(I) Catalysts 3,4-Dimethoxyfuran ( 1 ) readily reacts with acetylenedicarboxylates ( 2 ) at room temperature in a [2+4]-cycloaddition to give a mono-( 3 ) and several di-addition products. 90% of the latter consists of the endo-exo compound 4 . Under the influence of catalytic amounts of [Rh(CO)₂Cl]₂ the mixture of mono- and di-adducts in methanolic solution is smoothly transformed into endo-5,5,6-trimethoxy-7-oxabicyclo [2.2.1]hept-2-ene-2,3-dicarboxylate

1 Alle Verbindungen sind racemisch. Die Formeln stellen jeweils nur ein Enantiomeres dar.

(5) , 3-hydroxy-4,5-dimethoxyphthalate ( 6 ) and (I R *, 2 S *, 4 R *, 5 R *, 7 R *, 11 R *, 12 R *) -5,8,8,9,12-pentamethoxy-3,6-dioxatetracyclo [5.3.1.1 ^2,5 . 0 ^4,11 ]dodec-9-ene-1,11-dicarboxylate ( 7 ).     

Cycloadditionen von 3,4-Dimethoxyfuran an Dienophile

On cycloaddition reactions with 3,4-dimethoxyfuran We describe new cycloadditions of 3,4-dimethoxyfuran (3,4-DF, 1 ) with various dienophiles. In contrast to furan, the reaction of 3,4-DF with maleic anhydride gives exo- and endo-adducts at approximately the same rate. The thermodynamically more stable product is again the exo-product. Less active dienophiles lead also to mixtures of exo- and endo-adducts, except for citraconic anhydride (methylmaleic anhydride) which forms only the adduct with an endo-methyl group. Dimethylmaleic anhydride could not be reacted with 3,4-DF. All adducts with 3,4-DF contain a hidden 1,2-dicarbonyl group in the form of an endiolether. Its pronounced nucleophilic character allows a series of further additions. Noteworthy are the stereospecific cis-additions of halogens and the preparation of several acetals. Ozonolysis of the enolether in 4 allows the preparation of the hitherto unknown 2r, 3trans, 4trans, 5cis-tetrahydrofuran tetracarboxylic acid and derivatives thereof ( 5 and 6 ).     

Azokupplungen an 3,4-Dimethoxyfuran

Diazo coupling of 3,4-dimethoxyfuran with aryl diazonium ions 3,4-Dimethoxyfuran ( 1 ) easily reacts with aryl diazonium chloride in aqueous pyridine in an expected 1, 4-addition reaction. From the isolable primary addition product pyridine is displaced by alcohols, phenols or thiols to yield 4-alkoxy- or 4-phenoxy- or 4-thiophenoxy-derivatives of 2,3-dimethoxy-2-buten-4-olide ( 3 ). Attempts to convert them into azo compounds by a base catalysed 1, 6-elimination reaction failed. Oxidation of 3a and 3c with DDQ results in the formation of the mono p-nitrophenylhydrazone of 3, 4-dimethoxymaleic acid anhydride. On the other hand, the thiophenoxy compound 3g is smoothly converted by MnO₂ into the authentic furan-2-azobenzene derivative 5 .     

Nitrogen bridgehead compounds. Part 86. Synthesis and reactivity of 7,12-dihydropyrimido[1′,2′;1,2]pyrido[3,4-b]indol-4(6H)-ones. Debenzologues of rutaecarpine alkaloids

A series of 7,12-dihydropyrimido[1′2′:1,2]pyrido[3,4-b]mdole-4(6H)-ones was prepared by Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrirmdin-4-ones. Quantum chemical calculations (ab initio and AM1) indicate that position 3 of 7,12-dihydropyrimido[1′,2′:1,2]pyrido-[3,4-b]indole-4(6H)-one can be involved in electrophilic substitutions, while position 2 is sensitive towards nucleophilic attack. Bromination of 6-methyl-7,12-tetrahydropyrimido[1′,2′:1,2]pyrido-[3,4-b]indol-4(6H)-one 16 with bromine afforded 3-bromo derivative 25 , which was reacted with cyclic amines to give 2-ammo-7,12-dihydropyrirmdo[1′2′:1,2]pyrido[3,4-b]indol-4(6H)-ones 26–30 in an addition-elimination reaction. Vielsmeier-Haack formylation of compound 16 gave 12-formyl 31 and 3,12-diformyl 32 derivatives (an N-formyl-1-deaza derivative of nauclefidine alkaloid 34 ) at 60° and 100°, respectively. 3,12-Diformyl compound 32 was oxidized to 3-carboxyl derivative 33 with potassium permanganate. The quaternary salt 35 , obtained from compound 16 with dimethyl sulfate, suffered a ring opening on the action of aqueous sodium hydroxide. The new compounds have been characterized by elemental analyses uv, ¹H nmr and in some cases by ¹³C ruler, CD spectra and X-ray investigations.     

Selenium heterocycles XXVI. Synthesis of theino[3,4-b]benzofuran and selenolo[3,4-b] benzofuran. Two novel heterocycles

Starting from the readily available aryl 3-methyl-2-benzo[b] furyl ketones a series of 3-sub-stituted thieno[3,4-b] benzofurans and 3-substituted selenolo[3,4-b] benzofurans were prepared in high yield. The parent compound, thieno[3,4-b] benzofuran was prepared through the reaction of thioacetamide with 2-chloromethyl-3-formylbenzo[b] furan in moderate yield.     

Cycloadditionen von 3,4-Dimethoxyfuran an Benzochinone

Cycloadditions of 3,4-dimethoxyfuran with benzoquinones Cycloaddition of 3,4-dimethoxyfuran (3,4-DF, 1 ) with 1,4-benzoquinones furnishes isolable (2 + 4)-adducts in high yield. The crystalline products with benzoquinone, 2-methyl-benzoquinone, 2,3-dimethoxy-benzoquinone have endo-configuration, whereas 2,3-dimethyl-benzoquinone gives the exo-adduct 4c exclusively. Halogens (Cl₂, Br₂) add rapidly across the highly nucleophilic double bond of 3 or 4 in stereospecific cis-manner, and exclusively from the exo-side. The product 5c shows no sign of enolization to the hydroquinone; but with 3a and 3d the hydroquinones 6 were found. Methanolysis of 5 leads to the stable acetals 7 and 8 . On oxidation of the hydroquinones 7 the thermolabile quinones 10 were obtained. Preparative pyrolysis of 10a under relatively mild conditions (N₂, 200°, 0.1 Torr) gives tetramethoxy ethene ( 11 ) and isobenzofuran-4,7-quinone 12 , a yellowish, crystalline and stable compound.     

Synthesis of 1H-thieno[3,4-c]pyrazoles,thieno[3,4-b]furans,selenolo[3,4-b]furans and pyrrolo[3,4-d]thiazoles

Starting from the readily available aryl 2-methyl-5-phenyl-3-furyl ketones, 5-methyl-1H-1-phenylpyrazole-4-yl ketones and 4-methyl-2-phenyl-5-thiazolylcarboxaldehyde, a series of 2-phenyl-4-arylthieno[3,4-b]-furan, 2-phenyl-4-(p-methoxyphenyl)selenolo[3,4-b]furan, 4-aryl-1H-1-phenylthieno[3,4-c]pyrazole and 5-benzyl-2-phenylpyrrolo[3,4-d]thiazole were prepared in high yield.     

New Lignans from the Roots of Taiwania cryptomerioides Hayata

The five new lignans designated 3′,4′‐de‐O‐methylenehinokinin ( 1 ), taiwaninolide ( 2 ), 8′‐hydroxysavinin ( 3 ), isoguamarol ( 4 ), and 4′‐O‐methylsalicifolin ( 5 ), as well as the new 4‐(3,4‐dimethoxybenzyl)dihydro‐3‐(4‐hydroxybenzyl)furan‐2(3H)‐one ( 6 ) were isolated from the roots of Taiwania cryptomerioides, besides the three known compounds hinokinin ( 8 ), savinin ( 9 ), and 3,4‐de‐O‐methylenehinokinin ( 7 ). The structures of the new constituents were elucidated through chemical and spectral studies. A compound previously isolated from the heartwood of Chamaecyparis obtusa var. formosana was assigned structure 1 ; however, this structure has now been revised to be 3,4‐de‐O‐methylenehinokinin ( 7 ).     

Lignans from Phryma leptostachya L.

Three new lignans, haedoxan J ( 1 ), phrymarolin III ( 2 ), and phrymarolin IV ( 3 ), as well as eight known lignans, leptostachyol acetate, haedoxan A, 1‐(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)dihydro‐4‐(6‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, 4‐(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)dihydro‐1‐(4‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, 4‐[(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)oxy]dihydro‐1‐(6‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, leptostachyol acetate C, 4‐(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)dihydro‐1‐(6‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, and phrymarin II, were isolated from the plant Phryma leptostachya L. The structures of the new compounds were elucidated by analyzing their spectroscopic data and comparing with data reported in the literature.     

Fe<Subscript><Emphasis Type="Italic">n</Emphasis></Subscript> Clusters (<Emphasis Type="Italic">n</Emphasis> = 2–7) Interaction with Furan Ring: DFT Studies over Iron Surface Suitability for Furan Adsorption

The interaction of different iron clusters (Fe₂, Fe₃, Fe₄, Fe₅, Fe₆ and Fe₇) with furan compound was studied by density functional theory (DFT) and the results show that the compound possess suitable structural and electronic parameters for the metal adhesion. After analyzing the binding energy and molecular orbital studies, it is found that there is a bond between furan ring and metal. In the molecular orbital, since the HOMO localizes over furan ring, especially over C2=C3–C4=C5, the furan acts as donator (HOMO) and metal performs as acceptor (LUMO) in the interaction of furan with iron surface, transferring the high charge density mainly from the delocalization region of furan ring to the metal (L(σ) → Fe).     

Furan derivatives-IX : A convenient new method of arylation of furan reaction of diazoaminobenzenes with furan and isopentyl nitrite

A convenient new method for the arylation of furan with derivatives of diazoaminobenzene and isoamyl nitrite is described. Using this method the substituted 2-(X-phenyl)furan derivatives, where X is H, 4-CH₃, 4-Cl, 4-Br, 3-Cl, 3,4-diCl, 4-NO₂, 4-COOCH₃, 4-COOH, 4-Cl-3-CF₃ and 2-(3-pyridyl)furan were prepared. The reaction of methyl 4-aminobenzoate with furan and isopentyl nitrite gave (besides 2-(4-carbmethoxyphenyl)furan) 4,4′-dicarbmethoxydiazoaminobenzene, the structure of which was proved by mass spectrometry and by synthesis. This diazoaminobenzene derivative was unstable in the reaction medium and with isopentyl nitrite and furan at 30° gave 2-(4-carbmethoxyphenyl)furan. The mechanism of the reaction is discussed.     

2,3- and 3,4-Bis(diethoxyphosphorylmethyl)-5-tert-butylfurans

Reduction of 2-, 4-acetoxymethyl derivatives of 5-tert-butylfuran-3-carboxylic acid leads to the corresponding bis(hydroxymethyl)furans. Bis(chloromethyl)furans prepared from the latter were involvedin reaction with sodium diethyl phosphite. In the presence of two equivalents of a phosphorus-containing nucleophile, bis(phosphonomethyl)furans are formed. One equivalent of sodium diethyl phosphite reacts with 3,4-bis(chloromethyl)furan to give a mixture of 3-and 4-phosphorylated products in a 4.5:1 ratio in a low yield. The revealed difference in reactivity between the 3- and 4-chloromethyl groups demonstrates the importance of shielding of the chloromethyl group by the neighboring tert-butyl substituent. Examination of the ¹H NMR spectra of 3,4-bis(hydroxymethyl)-, 3,4-bis(chloromethyl)-, 3,4-bis(diethoxyphosphorylmethyl)-5-tert-butylfurans, and also specially prepared 5-tert-butyl-3-(diethoxyphosphorylmethyl)-4-(ethoxymethyl)-2-methylfuran established that the signal of the substituent neighboring to the tert-butyl group is always shifted downfield.     

Selenium heterocycles. XXXIII. Synthesis of thieno[3,4-b]furan,seleno[3,4-b]furan,thieno[3,4-b]indole and seleno[3,4-b]indole. four novel heterocycles

Starting from the readily available 2-methyl-3-benzoylfuran, 1-phenylthieno[3,4-b]furan and 1-phenyl-seleno[3,4-b]furan were prepared. Also, starting from phenyl 3-methylindol-2-yl ketone and aryl 2-methyl-indole-3-yl ketones a series of substituted thieno[3,4-b]indoles and substituted seleno[3,4-b]indoles were prepared.     

Regiospecific Displacement of the C-B Bond of Tris[4-(substituted)furan-3-yl]boroxines with C-Sn Bond and C-O Bond: Syntheses of 3,4-Disubstituted Furans and 4-Substituted-3(2H)-furanones,

Tris[4-(substituted)furan-3-yl]boroxines 2 , prepared from the corresponding 4-(substituted)-3-(trimethylsilyl) furan 1, were converted successfully to 4-(substituted)-3-(tributylstannyl)furans 3 through palladium-catalyzed cross-coupling reactions with tributylstannyl chloride. Palladium-catalyzed cross-coupling reactions of 3 with organohalides afforded 3,4-disubstituted furans 4 . Regiospecific iodination of 4-(trimethylsilyl)-3-((tributylstannyl) furan ( 3a ) gave 4-iodo-3-(trimethylsilyl)furan ( 5 ), which reacted with excess ethyl acrylate under a common Heck-condition to produce 2,3-bis(trans-ethoxycarbonylvinyl)-4-(trimethylsilyl)furan ( 6 ). A thermal 6-electrocyclic reaction followed by dehydration converted 6 into benzo[2,3-6]furan 8 . Oxidation of 2 generated the corresponding 4-substituted-3(2H)-furanones 9 .     

Novel hexahydrofuro[3,4-b]-2(1H)-pyridones from 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones

The title compounds 6 have been prepared in a one-step procedure from the corresponding 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones 4 in good yields. Quantum chemical calculations reveal a non-planar molecule with a distorted dihydropyridone ring and two favoured conformations. The 13C nmr data and theoretical calculations support a strong push-pull effect on the olefinic moiety.     

Synthesis of Two Natural Furan‐Cyclized Diarylheptanoids via 2‐Furaldehyde

Two natural diarylheptanoids, 2‐benzyl‐5‐(2‐phenylethyl)furan ( 1 ) and 2‐methoxy‐4‐{[5‐(2‐phenylethyl)furan‐2‐yl]methyl}phenol ( 2 ), were synthesized starting from 2‐furaldehyde. A Wittig reaction of 2‐furaldehyde with benzyltriphenylphosphonium bromide followed by reduction of the alkene C?C bond with Mg gave 2‐(2‐phenylethyl)furan ( 5 ). Lithiation of 5 with BuLi at ?78° followed by alkylation with benzyl bromide gave natural product 1 . In another approach, Friedel? Crafts acylation of compound 5 with benzoyl chloride followed by deoxygenation of the C?O group afforded 1 . The natural product 2 was also synthesized by acylation of 5 with 4‐acetoxy‐3‐methoxybenzoyl chloride ( 16 ) followed by deoxygenation and deacetylation.     

Structure-Activity Relationships of Oxygenated Morphinans. I. 4-Mono- and 3,4-dimethoxy-N-methylmorphinans and -N-methyl-morphinan-6-ones with unusually high antinociceptive potency. Preliminary communication

The antinociceptive potency and receptor affinity of several optically active aromatic mono- and di-oxygenated N-methylmorphinans and N-methylmorphinan-6-ones, prepared from natural morphine, were determined. Thus, in order of antinociceptive potency, 4-methoxy-N-methylmorphinan-6-one ≈ 3,4-dimethoxy-N-methylmorphinan-6-one ≈ 3,4-dimethoxy-N-methylmorphinan > 4-methoxy-N-methylmorphinan ≈ 4-acetoxy-N-methylmorphinan-6-one > 4-acetoxy-N-methylmorphinan ≈ 4-hydroxy-N-methylmorphinan-6-one ≈ 4-hydroxy-N-methylmorphinan. The 4-hydroxy compounds were slightly less potent than morphine, and the 4-methoxy and 3,4-dimethoxy compounds were found to have three times the potency of morphine. 4-Methoxy-N-methylmorphinan-6-one showed an opiate receptor affinity one-third that of morphine; this is a remarkably high affinity for a non-phenolic compound.     

Effects of β-cyclodextrin-based Schiff-base Zn(II) complexes: synthesis,physicochemical characterization and their role in alleviating oxidative stress related disorder

Abstract

Two water-soluble zinc(II) complexes of β-cyclodextrin-based Schiff bases, viz., mono-6-deoxy-6-(4-(5-chloro-2-hydroxybenzylideneamino)-3,4-diaminotolune)-β-cyclodextrin (4a) and mono-6-deoxy-6-(4-(5-nitro-2-hydroxybenzylideneamino)-3,4-diaminotolune)-β-cyclodextrin (4b) have been synthesized and characterized by different analytical and spectroscopic techniques. These Zn(II) complexes were analyzed for their possible activity against oxidative stress through various biochemical methods. A detailed antioxidant profile directly associated with inflammation related carcinogenesis and several oxidative stress related disorders have been prepared with a motive to evaluate the free radical scavenging activities of the synthesized complexes. The immune cell cytotoxic properties (through MTT assay) and in vitro assay for the evaluation of their antioxidant activities against hydroxyl radical, nitric oxide, singlet oxygen, peroxynitrate and hydrogen peroxide, etc. were investigated. Obtained results clearly demonstrated the role of reactive oxygen species in various phases of oxidative stress related diseases; thus, the antioxidant and free radical scavenging capacities of the two synthesized Zn(II) complexes seem to stand in support of their beneficial effects and novelty for the immune system.     

New Synthetic Approach to Naphtho[1,2‐b]furan and 4′‐Oxo‐Substituted Spiro[cyclopropane‐1,1′(4′H)‐naphthalene] Derivatives

A one‐step synthesis of ethyl 2,3‐dihydronaphtho[1,2‐b]furan‐2‐carboxylate and/or ethyl 4′‐oxospiro[cyclopropane‐1,1′(4′H)‐naphthalene]‐2′‐carboxylate derivatives 2 and 3 , respectively, from substituted naphthalen‐1‐ols and ethyl 2,3‐dibromopropanoate is described (Scheme 1). Compounds 2 were easily aromatized (Scheme 2). In the same way, 3,4‐dibromobutan‐2‐one afforded the corresponding 1‐(2,3‐dihydronaphtho[1,2‐b]furan‐2‐yl)ethanone and/or spiro derivatives 8 and 9 , respectively (Scheme 6). A mechanism for the formation of the dihydronaphtho[1,2‐b]furan ring and of the spiro compounds 3 is proposed (Schemes 3 and 4). The structures of spiro compounds 3a and 3f were established by X‐ray structural analysis. The reactivity of compound 3a was also briefly examined (Scheme 9).     

REVERSIBLE PHOTOCYCLOADDITION OF A 4',5'-DIHYDROPSORALEN DERIVATIVE WITH THYMINE

The photocycloaddition reaction between a 4′,5′-dihydropsoralen derivative and thymine was studied in solution using a synthetic bichromophoric model 8 in which the two rings are associated by a tetramethylene chain. In water this model molecule exhibits intramolecular ring-ring stacking interactions as evidenced by UV and NMR spectroscopies. Irradiation at 365 nm at usual concentrations ( 5.10^?-⁴M) leads exclusively to a regio- and stereo-selective dimerization reaction involving the 3,4 double bonds of the psoralen moities. Extreme dilutions (ca 2.10^?-⁵M) were necessary to observe the intramolecular reaction which results in the exclusive formation of a 3,4 cb-anti adduct. This reaction is completely reversed by irradiation at 254 nm. These results are discussed with regard to the behavior of the homologous models in which the furan part of the psoralen ring is not hydrogenated, These latter compounds also lead exclusively to a 3,4 cis-anti adduct. It appears that saturation of the furan ring increases strongly the quantum yield of the photaddition at 365 nm (0.01 → 0.18) and that the triplet excited state of the 4′,5′-dihydropsoralen is involved in the photoaddition.