Antileukemic α-pyrone derivatives from the endophytic fungus Alternaria phragmospora

Four new (1–4) and two known (5 and 6) α-pyrone derivatives have been isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea, leaves. The isolated compounds were chemically identified to be 5-butyl-4-methoxy-6-methyl-2H-pyran-2-one (1), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one (2), 5-(1-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (3), 4-methoxy-6-methyl-5-(3-oxobutyl)-2H-pyran-2-one (4), 5-(2-hydroxyethyl)-4-methoxy-6-methyl-2H-pyran-2-one (5), and 5-[(2E)-but-2-en-1-yl]-4-methoxy-6-methyl-2H-pyran-2-one (6). Compounds 2 and 4 showed moderate antileukemic activities against HL60 cells with IC₅₀ values of 2.2 and 0.9 μM and against K562 cells with IC₅₀ values of 4.5 and 1.5 μM, respectively.     

New,Convenient, One-Pot Method for the Synthesis of Thiazolyl-pyrazolones from Dehydroacetic Acid Derivative via a Multicomponent Approach

A convenient one-pot method for the synthesis of thiazolyl-pyrazolones was described in excellent yields. Reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one with thiosemicarbazide and ethyl 2-(2-arylhydrazono)-3-oxobutanoates in anhydrous ethanol under reflux conditions afforded the corresponding 4-(2-arylhydrazono)-1-(4-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)thiazol-2-yl)-3-methyl-1H-pyrazol-5(4H)-one in good yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, infrared, ¹H NMR, and mass spectroscopic studies.     

Four component tandem Knoevenagel–Michael strategy for the assembly of arylaldehydes,N,N'-dimethylbarbituric acid, 4-hydroxy-6-methyl-2H-pyran-2-one and morpholine into unsymmetrical scaffold with three different heterocyclic rings

A new type of four component tandem Knoevenagel–Michael reaction has been found consisting in the assembly of benzaldehydes, N,N'-dimethylbarbituric acid, 4-hydroxy-6-methyl-2H-pyran-2-one and morpholine in alcohols, other organic solvents or water at room temperature without catalyst or any other additives, which results in the selective formation of unsymmetrical scaffold with three different heterocyclic rings in 63–98% yields. The crystal structure of morpholinium 5-[(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)(4-nitrophenyl)methyl]-1,3-dimethyl-2,6-dioxo-1,2,3,4-tetrahydropyrimidin-6-olate has been confirmed by X-ray diffraction.     

10-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-methyl-1H,10H-pyrano[4,3-b] chromen-1-ones from a pseudo-multicomponent reaction and evaluation of their antioxidant activity

A series of novel 10-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-methyl-1H,10H-pyrano[4,3-b]chromen-1-ones were synthesized by a pseudo-three-component reaction of 4-hydroxy-6-methyl-2-oxo-2H-pyran-2-one (TAL) with 2-hydroxyarylaldehydes using different acids as catalysts and solvents. The approach relies on a regioselective cascade reaction involving two molar equiv of the TAL iteratively acting as active methylene in a Knoevenagel condensation and in a Michael addition. The antioxidant activity of the synthesized compounds were determined using the DPPH scavenging assay, being the results dependent on the nature and number of chromone substituents. The compound bearing an ortho-dihydroxy (catechol) moiety showed excellent activity at lower concentrations, while derivatives bearing alkoxy groups as substituents present pro-oxidant activity.     

A novel and green synthesis of kojic acid derivatives in ionic liquid [bmim]BF4

A series of 3-(3-hydroxy-6-methyl-4-oxo-4H-pyran-2-yl)-3-phenylpropanamide derivatives were synthesized efficiently by one-pot condensation of aromatic aldehydes, meldrum’s acid, allomaltol, and ammonium acetate in ionic liquid [bmim]BF₄. The novel synthesis method offers the advantage of operational simplicity, mild reaction conditions, short reaction time, higher yields, and environmental friendliness.     

Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel–Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones, from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.     

Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of strong CH-acids: one-pot synthesis of highly functionalized annulated 4H-pyrans

The highly reactive 1:1 adduct, produced from the reaction between dialkyl acetylenedicarboxylates and alkyl isocyanides, was trapped by strong cyclic CH-acids such as 4-hydroxy-6-methyl-2H-pyran-2-one or 4-hydroxycoumarin to yield dialkyl 2-(alkylamino)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3,4-dicarboxylates or dialkyl 7-methyl-2-(alkylamino)-5-oxo-4H,5H-pyrano[4,3-b]pyran-3,4-dicarboxylates in good yields at room temperature.     

A simple and convenient synthesis of 3-[5-(trifluoromethyl)-1,2,3-triazol-4-yl]cinnamic acids from 4-aryl-6-(trifluoromethyl)-2H-pyran-2-ones and sodium azide

4-Aryl-6-(trifluoromethyl)-2H-pyran-2-ones and ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates react with sodium azide to produce highly functionalized CF₃-1,2,3-triazoles: 3-[5-(trifluoromethyl)-1,2,3-triazol-4-yl]cinnamic acids and monoethyl esters of [5-(trifluoromethyl)-1,2,3-triazol-4-yl]arylmethylidene malonic acids.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

Summary. A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Synthesis of substituted benzofurans by condensation of arylglyoxals with enols and phenols

A convenient method for the synthesis of previously unknown substituted 3-hydroxy-5,5- dimethyl-2-(2-arylbenzofuran-3-yl)cyclohex-2-enones, 4-hydroxy-6-methyl-3-(2-arylbenzofuran- 3-yl)-2H-pyran-2-ones, and 2-hydroxy-3-(2-arylbenzofuran-3-yl) naphthoquinones was developed based on the reaction of 3,4-methylenedioxyphenol or 2-naphthol with pyridinium salts obtained by multicomponent condensation of arylglyoxals with carbo- or heterocyclic enols and 4-dimethylaminopyridine.     

Chemo-, regio- and stereospecific addition of adenine and 8-azaadenine to α,β-acetylenic γ-hydroxy nitriles: a short-cut to novel acyclic adenosine analogues

Adenine (9H-purin-6-amine) adds readily to available α,β-acetylenic γ-hydroxy nitriles under mild conditions (molar ratio 1:1, K₂CO₃, DMF, rt, 10 min) to afford chemo-, regio- and stereospecifically (Z)-3-(6-amino-9H-purin-9-yl)-4-hydroxy-4-alkyl-2-alkenenitriles, novel functionalized acyclic nucleoside analogues (95-98% yield). Under similar conditions (K₂CO₃, DMF, rt, 1 h), 8-azaadenine (3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine) reacts with 4-hydroxy-4-methyl-2-pentynenitrile nonselectively at the 7-, 8- and 9-positions to give the corresponding adducts in a 1:10.5:9 ratio, the total yield being 81%. Chemo-, regio- and stereospecific addition of 8-azaadenine to the above α,β-acetylenic γ-hydroxy nitriles leading to (Z)-3-(7-amino-2H-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-4-hydroxy-4-alkyl-2-alkenenitriles in 44-90% yield is attained when the reaction is carried out without solvent in the presence of Et₃N (30 mol %), the molar ratio of 8-azaadenine:α,β-acetylenic nitriles being 1:2.0 (rt, 12-38 h).     

Synthesis of Urinary Metabolites of Retinoic Acid

Urinary metabolites 5-methyl-5-[2-(2,6,6-trimethyl -3-oxo-1-cyclohexen-1-yl)-vinyl]-2-tetrahydrofuranone (1) and 5-[2-(6-hydroxymethyl-2, 6-dimethyl-3-oxo-1- cyclohexen-1-yl)vinyl]-5-methyl-2-tetrahydrofuranone (2) of retinoic acid have been synthesized from 4-[2,2,6-trimethyl-3-(tetrahydro-2 H -pyran-2-yl)oxy-1-cyclohexen-1-yl]-3-buten-2-one (4) and methyl 2-(3,3-ethylenedioxy-1-butenyl)-1, 3-dimethyl-4-oxo-2-cyclohexene-1-carboxylate (5) .     

Multi-component condensation of 4-hydroxy-6-methyl-1H-pyridin-2-one with carbonyl compounds and Meldrum’s acid

A convenient method for the synthesis of earlier unknown substituted derivatives of 4-aryl-7-methyl-4,6-dihydro-3H-pyrano[3,2-c]pyridine-2,5-dione and ethyl 3-(4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)-3-arylpropionate was developed based on the multi-component condensation of 4-hydroxy-6-methyl-1H-pyridin-2-one, Meldrum’s acid, and carbonyl compounds.     

Five-membered dioxoheterocycles: XCIX. Reaction of 1-aryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones with indoles. Crystal and molecular structure of substituted 2-(indol-3-yl)pyrrole

1-Aryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones react with indole and 2-methylindole with the formation of methyl 1-aryl-3-aroyl-4-hydroxy-2-(1H-indol-3-yl)-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates. Crystal and molecular structure of methyl 3-benzoyl-4-hydroxy-2-(2-methyl-1H-indol-3-yl)-5-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-2-carboxylate was examined.     

Unexpected course of rearrangement of substituted S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides

Three series of S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides differing in substitution at the isothiuronium moiety (none, one or two methyl groups) and at the benzene ring were prepared and characterized. These salts were then treated with various bases (acetate, triethylamine, Na₂CO₃) to give either 1-hydroxy-3-oxo-1,3-dihydro-2H-isoindol-2-carbothioamides or the product of S to N isobenzofuranone-3-yl migration, i.e., 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas. If ammonia was used in reaction with N,N′-dimethyl isothiuronium salts then 3-hydroxy-2,3-dihydro-1H-isoindol-1-ones were formed together with 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas in parallel reaction with the yields increasing with ammonia concentration. The formation of isoindolones takes place in two steps with an aldehyde intermediate, which can be trapped with N,N-dimethylhydrazine.     

The reactions of 4-hydroxy-2-pyrones with 2-hydroxybenzaldehydes. A note of warning

The reaction between 2-hydroxybenzaldehyde and 4-hydroxy-6-methyl-2-pyrone (triacetic acid lactone) affords 3-acetoacetyl-2-chromenone, 7 , instead of 3-(2-hydroxybenzylidene)-6-methyl-3,4-dihydro-2H-pyran-2,4-dione, 6 . The structures previously reported in the literature for the products formed in the reactions of 4-hydroxy-2-chromenone with 2-hydroxybenzaldehydes in a molar ratio 1:1 are considered erroneous. Thus, the previously reported 3-(2-hydroxybenzylidene)chroman-2,4-dione, 10 , should be formulated as 3-(2-hydroxybenzoyl)-2-chromenone, 11 .     

An experimental and a DFT study on the synthesis, spectroscopic characterization, and reactivity of the adducts of dimethyl- and diphenyltin(IV) dichlorides with γ-pyrones [4H-pyran-4-one (PYR) and 2,6-dimethyl-4H-pyran-4-one (DMP)]: Crystal structure of Ph2SnCl2(PYR)

The Sn(IV) R₂SnCl₂(γ-pyrone)_n [R = Me or Ph; γ-pyrone = 4H-pyran-4-one (PYR) or 2,6-dimethyl-4H-pyran-4-one (DMP); n = 1 or 2] adducts have been synthesized and investigated. The adducts Ph₂SnCl₂(PYR) (1), Me₂SnCl₂(PYR)₂ (2), Ph₂SnCl₂(DMP) (3) and Me₂SnCl₂(PYR)(PNO) (4), (PNO = 4-methylpyridine N-oxide) have been prepared by the addition of the corresponding γ-pyrone to chloroform solution of R₂SnCl₂. The new compounds have been characterized by elemental analysis and spectroscopic (IR, ¹H, ¹³C NMR and Mössbauer) means. The single-crystal diffraction study of 1 shows the Sn(IV) to be five-coordinate, [Sn-O and Sn-Cl(1), Sn-Cl(2) distances of 2.3190(13) and 2.4312(6), 2.3653(7), respectively], and the Cl-Sn-Cl bond angle to be 91.17°. The reactivity of 2 towards bipy, Ph₃PO, QNO (Q = quinoline) resulted in complete displacement of PYR and formation of already known compounds whereas, the PNO displaced only one equivalent of PYR, causing the preparation of the new mixed complex 4, possibly through a S_N¹ formation mechanism. DFT/B3LYP molecular orbital calculations were carried out for the 1-4 complexes, their precursors, Ph₂SnCl₂, (5) and Me₂SnCl₂, (6) and the ligands, PYR, DMP and PNO in an attempt to explain the structures and reactivity of the complexes. Optimized resulting geometries, vibrational frequencies, and the electron-accepting ability of the complexes and the precursors towards nucleophiles are discussed.     

Synthesis,structure elucidation and plants growth promoting effects of novel quinolinyl chalcones

The readily synthesized 3-(4-Hydroxy-1-methyl-1,2-dihydro-2-oxoquinolin-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyd (5) and 3-(2-Oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (6) were utilized as a convenient starting precursor materials for synthesis of novel enone system 4-hydroxy-1-methyl-3-(4-(2H-2-oxo-chromen-3-yl)prop-2-enoyl)-1-phenyl-1H-pyrazol-4-yl)quinolin-2(1H)-one (7) and4-hydroxy-1-methyl-3-(2E)-3-(3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)acryloyl)quinolin-2(1H)-one (8). Simple homonuclear NOE experiment (NOESY 1D) method was performed for structure elucidation of the novel quinolinyl chalcones. The synthesized compounds have been estimated for their effect of growth on some selective crop of plants (Hibiscus, Mint and Basil).     

Study of protonation and Zn(II), Cd(II), Cu(II) and Mn(II) complexation with a glutamic acid N-pyrimidine derivative: Crystal structure of a neutral Cd(II) complex of the bianionic ligand

The compound N-(4-amino-1-methyl-5-nitroso-6-oxo-1,6-dihydropyrimidin-2-yl)-(s)-glutamic acid (H₃L) was synthesised and structurally characterised by analytical methods and ¹H, ¹³C and ¹⁵N NMR spectroscopy. This compound (H₃L) shows the same topology as other model receptors previously used to develop chemical functionalization at the surface of an active carbon when they adsorb on it. Protonation of H₃L and its coordination ability towards Cd²⁺, Zn²⁺, Cu²⁺ and Mn²⁺ ions in water solution was also studied by potentiometric methods, UV–Vis and ¹H, ¹³C NMR spectroscopies. The obtained results allow us to fit the operative conditions for the use of the activated carbon–H₃L adsorbent for the retaining of the above-mentioned metal ions in aqueous solutions. The molecular structure of {[Cd(HL)H₂O] · 3H₂O}_n was solved by single-crystal X-ray diffraction methods.