The use of umbelliferone in the synthesis of new heterocyclic compounds

New coumarin derivatives, namely 7-[(5-amino-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one, 5-[(2-oxo-2H-chromen-7-yloxy)methyl]-1,3,4-thiadiazol-2(3H)-one, 2-[2-(2-oxo-2H-chromen-7-yloxy)acetyl]-N-phenylhydrazinecarbothioamide, 7-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one and 7-[(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)methoxy]-2H-chromen-2-one were prepared starting from the natural compound umbelliferone. The newly synthesized compounds were characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR).     

Reaction of Dimethyl Sulfoxide with 4-Acyloxycoumarins

Dimethyl sulfoxide converts 4-acetoxycoumarin (1) exclusively to 2-(2-hydroxybenzoyl)-2-[(methylthio)methyl]-2,3-dihydro-4 H-furo[3,2-c]chromen-4-one (3) at 180°C under a nitrogen atmosphere, but in the absence of nitrogen, the products obtained are dicoumarol and its dehydrative cyclization products 7 H-bis[1]benzopyrano[4,3-b: 3′,4′-c]pyran-6,8-dione (9) and (3). Under similar conditions, 4-benzoyloxycoumarin (1a) affords benzoic acid, 4-hydroxy-3-({2-[(methylthio)methyl]-3-oxo-2,3-dihydro-1-benzofuran-2-yl}methyl)-2H-chromen-2-one (7), and 3-(2-hydroxybenzoyl)-3,4-dihydro-2H,5H-pyrano[2,3-b] chromen-5-one (8).     

Synthesis of some new types of 3-coumarinyl-substituted pyrazolopyrimidines and imidazothiazoles

The treatment of 3-[3-(dimethylamino)-1-oxo-2-propenyl]chromen-2-ones with 3-amino-4-cyanopyrazole gives 7-(2-oxo-2H-chromen-3-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitriles. The reaction of 3-(2-bromoacetyl)coumarins with 2-amino-4-(methoxycarbonylmethyl)thiazole and 2-amino-4-methylthiazole gives methyl 2-(6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b]thiazol-3-yl)acetate and 3-(2-methylimidazo[2,1-b]thiazol-6-yl)-2H-chromen-2-ones, respectively. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 465–471, March, 2008.     

Synthesis of Hybrid Compounds on the Basis of 4-[(1-Oxo-3,4-dihydro-2H-naphthalen-2-ylidene)methyl]benzoic acid

Russian Journal of Organic Chemistry - The reactions of 4-[(1-oxo-3,4-dihydro-2H-naphmalen-2-ylidene)methyl]benzoic acid with 3-(1,3-dioxobutane-1-yl)-2H-chromen-2-one in the presence of...     

Metabolism of ipriflavone (TC-80) in rats

Metabolic studies of ipriflavone (TC-80) in rats by gas-liquid chromatography-mass spectrometry led to the characterization of the following metabolites: the parent compound, 7-hydroxy-3-phenyl-4H-1-benzopyran-4-one, 7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one, 3-(4-hydroxyphenyl)-7-isopropoxy-4H-1-benzopyran-4-one, 2-(3-phenyl-4-oxo-4H-1-benzopyran-7-yl)oxypropionic acid, 2-[3-(4-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7-yl]oxypropionic acid and 2-[3-(3-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7-yl]oxypropionic acid. From the metabolites identified, TC-80 was shown to be metabolized primarily by oxidation. In vitro study using tissue slices of rats indicated that the above metabolic changes occurred exclusively in the liver. It was also demonstrated that the compound did not undergo metabolic conversion by gut flora of rats.     

Novel One-Pot Multicomponent Synthesis of Substituted 2,3-Dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones and Substituted 3-[3-(N′-Benzylidene-hydrazino)-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones

A one-pot procedure has been developed for the synthesis of substituted 2,3-dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones by reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and phthalic anhydrides in acetic acid medium. Similarly, a one-pot, three-component synthetic procedure has been developed for substituted 3-[3-(N¹-benzylidene-hydrazino)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones from 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and various aromatic aldehydes in absolute ethanol and a few drops of glacial acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Aryloxyacetic acid diuretics with uricosuric activity. II. Substituted [(4-oxo-4H-1-benzopyran-7-yl)oxy]acetic acids and the related compounds.

Di- and tri-substituted [(4-oxo-4H-1-benzopyran-7-yl)oxy]acetic acids, and 4-oxo-3-phenyl-4H-furo[2,3-h]-[1]benzopyran-8-carboxylic acid were synthesized and tested for natriuretic and uricosuric activities. Among the compounds tested, 3,5-disubstituted [(4-oxo-4H-1-benzopyran-7-yl)oxy]acetic acids (6c-f, h, n and x) showed potent natriuretic and uricosuric activities, whereas 4-oxo-3-phenyl-4H-furo[2,3-h][1]benzopyran-8-carboxylic acid (6dd) possessed only potent natriuretic activity. The structure-activity relationships are also discussed.     

A Facile One-Step Synthesis of New Types of 8-Thiazolyl and 8-Thiadiazinyl Coumarins

N-[4-(7-Methoxy-4-methyl-2-oxo-2H-chromen-8-yl)-thiazol-2-yl]-guanidine ( 2 ) has been prepared by the condensation of 4-methyl-7-methoxy-8-(2-bromoacetyl)coumarin ( 1 ) with guanylthiourea. 4-Methyl-7-methoxy-8-[2-(N′-(1-phenyl-ethylideneisopropylidene)-hydrazino]-thiazol-4-yl]chromen-2-ones ( 3 , 4 , and 5 ) have been prepared by reaction of 4-methyl-7-methoxy-8-(2-bromoacetyl) coumarin ( 1 ) and thiosemicarbazide in presence of acetophenone or acetone without any solvent. The formation of these compounds was further confirmed by the condensation of acetophenone/acetone thiosemicarbazones with 4-methyl-7-methoxy-8-(2-bromoacetyl)coumarin ( 1 ) in anhydrous ethanol in a two-step process. Similarly 8-[2-[N′-(benzylidene)hydrazine]-thiazol-4-yl]-7-methoxy-4-methyl-chromen-2-ones ( 6 , 7 , and 8 ) have been prepared by the condensation of 4-methyl-7-methoxy-8-(2-bromoacetyl)chromen-2-one with thiosemicarbazide and various aromatic aldehydes in a single step without any solvent. The formation of these compounds was further confirmed by the condensation of appropriately substituted benzaldehyde thiosemicarbazones with 4-methyl-7-methoxy-8-(2-bromoacetyl)coumarin in anhydrous ethanol. 4-Methyl-7-methoxy-8-(2-bromoacetyl) chromen-2-one (1) upon condensation with 3,5-dimercapto-4-amino-s-triazole in anhydrous ethanol resulted in the formation of 8-(3-mercapto-3H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl)-7-methoxy-4-methyl chromen-2-one (9). This compound ( 9 ) on reaction with various alkyl and phenacyl halides in anhydrous ethanol gave corresponding 4-methyl-7-methoxy-8-[3-(2-oxo-substituted sulphanyl)-7H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl]chromen-2-ones ( 10 to 18 ). The structures of newly prepared compounds have been confirmed from analytical and spectral data.     

Synthesis of aromatic carbamates derivatives with a chromen-2-one fragment

Condensation of methyl N-(3-hydroxyphenyl)carbamate with ethyl trifluoromethylacetoacetate, 2-methoxyethyl acetoacetate in the presence of conc. sulfuric acid, and also with acetonedicarboxylic acid formed in situ from citric acid under the action of conc. sulfuric acid afforded chromene derivatives. The esterification of 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}acetic acid with methanol in the presence of TsOH provided the corresponding ester. The oxidation of its α-methylene group with selenium dioxide led to the formation of methyl 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}-2-oxo-acetate entering into a condensation with o-phenylenediamine resulting in a derivative with a dihydroquinoxaline fragment. The reaction of phenyl N-(4-formylphenyl)carbamate with 3-acetyl-2H-chromen-2-one in butanol in the presence of catalytic quantity of piperidine and acetic acid furnished 4-[(E)-3-oxo-2H-chromen-3-yl)-1-propenyl]phenyl N-phenylcarbamate.     

Synthesis and screening of some novel substituted indoles contained 1,3,4-oxadiazole and 1,2,4-triazole moiety

A series of novel 3-[5-(1H-indol-3-yl-methyl)-2-oxo-[1,3,4]oxadiazol-3-yl]propionitrile(5),3-[4- amino-3-(1H-indol-3-yl-methyl)-5-oxo-4,5-dihydro-[1,2.4]triazol-1-yljpropionitrile(6),3-[5-(1H- indol-3-yl-methyl)-2-thioxo-[1,3,4]oxadiazol-3-yl]propionitrile(7) and 3-[4-amino-3-(1H-indol-3-yl-methyl) -5-thioxo-4,5-dihydro-[1,2,4]triazol-l -yljpropionitrile(8) were synthesized in good yields from the intermediate(1H-indol-3-yl)-acetic acid N’-(2-cyanoethyl)hydrazide(4).The chemical structures of the newly synthesized compounds were elucidated by their IR,~1H NMR and MS.Further,all the compounds were screened for their antimicrobial activity against Gram-positive,Gram-negative bacteria and also tested their ability toward anti-inflammatory activity.     

Molecular Diversity from the L-Proline-Catalyzed,Three-Component Reactions of 4-Hydroxycoumarin,Aldehyde, and 3-Aminopyrazole or 1,3-Dimethyl-6-aminouracil

The three-component reaction of 4-hydroxycoumarin, aldehyde, and aminopyrazole in the presence of a catalytic amount of L-proline in ethanol under reflux conditions provided the cyclized product (dihydrochromeno[4,3-b]pyrazolo[4,3-e]pyridine-6(7H)-one), whereas under similar reaction conditions, replacing aminopyrazole by 1,3-dimethyl-6-aminouracil provided the acyclic three-component product (6-amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione). This method is metal free and atom economical, and avoids column chromatographic purification as all the products can be purified by recrystallization.     

Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives

Substitution at the 7-position of the chromen-4-one pharmacophore of 8-(dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one NU7441, a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, with allyl, n-propyl or methyl enabled the resolution by chiral HPLC of atropisomers. Biological evaluation against DNA-PK of each pair of atropisomers showed a marked difference in potency, with biological activity residing exclusively in the laevorotatory enantiomer.     

三唑类白杨素衍生物的设计、合成及其抗增殖活性研究

合成了2个系列的白杨素衍生物,采用噻唑蓝(MTT)法测试了所有化合物针对六种肿瘤细胞的体外抗增殖活性,包括MGC-803, BEL-7402, HepG2, HeLa, A549以及SGC-7901细胞.实验结果显示, 7-[1-(3-氟苯基)-1H-1,2,3-三唑-4-甲氧基]-白杨素(1c)与7-[1-(2-氯苯基)-1H-1,2,3-三唑-4-甲氧基]-白杨素(1g)针对MGC-803细胞的活性与先导化合物白杨素及阳性对照药5-氟尿嘧啶相比显著提高.因此,化合物1c与1g具有深入研究用以开发抗癌药物的潜能.     

Design and the synthesis of 1-heteroaryl-1,2,3-triazoles connected to coumarins via ether linker

In this paper, we report an efficient and versatile methodology for the synthesis of a series of novel heteroaryl-1,2,3-triazoles connected to 4-methylcoumarin (4-methyl-2H-chromen-2-one) via oxymethylene linker. The desired molecules were accessed by both two-step synthesis and the one-pot copper catalyzed cycloaddition reaction of heteroaromatic azides with coumarin containing acetylenes. The developed protocol was found to be facile and effective for preparing a series of novel heteroaryl-1,2,3-triazole-coumarin conjugates in excellent yields. Practical utility of one-pot protocol has been confirmed by the successful gram-scale synthesis of 1,3-Dimethyl-6-(4-[([4-methyl-2-oxo-2H-chromen-7-yl]oxy)methyl]-1H-1,2,3-triazol-1-yl)pyrimidine-2,4(1H,3H)-dione.     

Rhenium tricarbonyl core complexes of thymidine and uridine derivatives

Thymidine and uridine were modified at the C2' and C5' ribose positions to form amine analogues of the nucleosides (1 and 4). Direct amination with NaBH(OAc)3 in DCE with the appropriate aldehydes yielded 1-{5-[(bis(pyridin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L1), 1-{5-[(bis(quinolin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L2), and 1-[3-(bis(pyridin-2-ylmethyl)amino)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidine-2,4-dione (L5), while standard coupling procedures of 1 and 4 with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (2) and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid (3) in the presence of HOBT-EDCI in DMF provided a second novel series of bifunctional chelators: 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L3), 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L4), 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L6), and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L7). The rhenium tricarbonyl complexes of L1-L4, L6, and L7, [Re(CO)3(LX)]Br (X=1-4, 6, 7: compounds 5-10, respectively), have been prepared by reacting the appropriate ligand with [NEt4][Re(CO)3Br3] in methanol. The ligands and their rhenium complexes were obtained in good yields and characterized by common spectroscopic techniques including 1D and 2D NMR, HRMS, IR, cyclic voltammetry, UV, and luminescence spectroscopy and X-ray crystallography. The crystal structure of complex 6.0.5NaPF6 displays a facial geometry of the carbonyl ligands. The nitrogen donors of the tridentate ligand complete the distorted octahedral spheres of the complex. Crystal data: monoclinic, C2, a = 24.618(3) A, b = 11.4787(11) A, c = 15.5902(15) A, beta = 112.422(4) degrees , Z = 4, D(calc) = 1.562 g/cm3.     

Iodine catalyzed synthesis of the chromene derivatives in one-pot

Iodine catalyzed one-pot reactions of salicylaldehyde and dimolecular 1 H-indene-1,3(2H)-dione,barbituric acids,4-hydroxycoumarin, or 4-hydroxy-6-methylpyran-2-one were performed and provided a rapid,convenient and general approach to synthesize the chromene derivatives.2-(11-Oxo-10,11-dihydroindeno[l,2-b]chromen-10-yl)-1H-indene-1,3(2H)-diones P1-P4 and 10-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-methylpyrano[4,3-6]chromen-1(10H)-ones P8-P9 were unprecedentedly prepared and structurally identified by NMR and Mass.The confirmation of structure by single crystal X-ray crystallography is reported for P3.     

微波辐射下4,6-二羟基嘧啶与醛的反应研究

以甲胺为催化剂、醋酸为溶剂, 微波促进下芳香醛与两分子4,6-二羟基嘧啶反应得到6-羟基-5-[(4-羟基-6-氧代-1,6-二氢嘧啶-5-基)芳甲基]嘧啶-4(3H)-酮衍生物.     

One Pot,Multi-component Synthesis of 3-[（4-Aryl-thiazol-2-yl）-hydrazono]-1,3-dihydro-indole-2-one

A series of 3-[（4-phenyl-thiazol-2-yl）-hydrazono]-1,3-dihydro-indole-2-one（4a-4g） and 3-{[4-（2-oxo2H-chromen-3-yl）-thiazol-2-yl]-hydrazono}-1,3-dihydro-indol-2-one（6a-6d） has been prepared in a one-step procedure from condensation reaction of isatin（1）,thiosemicarbazide（2） and bromoacetophenones（3）/or 3-（2-bromoacetyl）coumarins（4）.The method provides a simple and efficient route to prepare the compounds in good yields and in a short experimental time as compared to its stepwise procedure.     

8-羟基喹啉席夫碱衍生物及其金属配合物的合成及荧光性质研究

设计合成了三种新的8-羟基喹啉席夫碱衍生物4-(8-羟基喹啉-5-亚胺甲基)-7-甲氧基苯并吡喃-2-酮(3a),4-(8-羟基喹啉-5-亚胺甲基)-7-己氧基苯并吡喃-2-酮(3b)和4-(8-羟基喹啉-5-亚胺甲基)-7-十八烷氧基苯并吡喃-2-酮(3c)及其铝、锌配合物,产物结构经1H(13C)NMR,MS,HRMS,IR和元素分析表征,研究了它们的荧光发光性能.     

Synthesis of 3-amino-3,4-dihydroquinazolin-4-one derivatives from anthranilic acid hydrazide and dicarboxylic acids

Treatment of anthranilic acid hydrazide with 2 equiv of ethoxalyl chloride gave the corresponding diester which underwent cyclization in acetic anhydride to produce ethyl 3-(ethoxalylamino)-4-oxo-3,4-dihydroquinazoline-2-carboxylate. Acylation of anthranilic acid hydrazide first with succinic anhydride and then with ethoxalyl chloride led to the formation of 4-[2-(2-{[ethoxy(oxo)acetyl]amino}benzoyl)hydrazino]-4-oxobutanoic acid whose cyclization in acetic acid afforded N-(2-ethoxycarbonyl-4-oxo-3,4-dihydroquinazolin-3-yl)succinamic acid, while in acetic anhydride ethyl 3-(2,5-dioxopyrrolidin-1-yl)-4-oxo-3,4-dihydroquinazoline-2-carboxylate was obtained. The latter was brought into reactions with amines and hydrazine hydrate and alkaline hydrolysis. Acylation of 2-[2-(2-aminobenzoyl)hydrazinocarbonyl]benzoic acid with ethoxalyl chloride gave ethyl N-[2-(phthalimidocarbamoyl)phenyl]oxamate, and with succinic anhydride, 3-[4-oxo-3-phthalimido-3,4-dihydroquinazolin-2-yl]propionic acid. 4-[2-(2-Aminobenzoyl)hydrazino]-4-oxobutanoic acid reacted with phthalic anhydride in boiling acetic acid to give phthalazino[1,2-b]quinazoline-5,8-dione via elimination of succinic acid residue.