Six new 2-(2-phenylethyl)chromones from Agarwood

Six new chromones, 6-methoxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyllchromone (2), 6,8-dihydroxy-2-(2-phenylethyl)chromone (3), 6-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]chromone (4), 6-hydroxy-2-[2-(2-hydroxyphenyl)ethyl]chromone (5), 7-hydroxy-2-(2-phenylethyl)chromone (6), and 6-hydroxy-7-methoxy-2-(2-phenylethyl)chromone (7) were isolated from the ether extract of agarwood in addition to a known compound, 2-(2-phenylethyl)chromone or flidersiachromone (1). Their structures were determined by spectroscopic methods including UV, IR, and NMR spectral data and comparisons with the calculated values using the hydroxyl and methoxyl substituent increments of the chromone ring.     

Isolation and Characterization of Anti-Inflammatory Chromones from Imperata cylindrica var. major

Chemistry of Natural Compounds - One new chromone, 5-hydroxy-8-O-β-D-glucopyranosyl-2-(2-phenylethyl)chromone (1), along with 13 known ones (2–14) were obtained and identified from a 70%...     

Three 2-(2-phenylethyl) chromones and two terpenes from agarwood

A new Chromone, 7,8-dimethoxy-2-[2-(3'-acetoxyphenyl)ethyl]chromone (1) was isolated from an acetone extract of the Cambodian agarwood along with two known chromones, 6-methoxy-2-(2-phenylethyl)chromone (2) and 6,7-dimethoxy-2-(2-phenylethyl)chromone (3). In addition, an abietane ester (4) and the sesquiterpene dehydrofukinone (5) were isolated from the agarwood oil of the same origin. Structural elucidation of all isolated compounds was made based on IR, 1H and 13C NMR spectroscopic data.     

Derivatives of 4-hydroxy-5,6,7,8-tetrafluorocoumarin in reactions with o-aminothiophenol

The derivatives of 4-hydroxy-5,6,7,8-tetrafluorocoumarin in reactions witho-aminothiophenol yield products of S-substitution at C⁷ atom, 7-substituted 5,6,8-trifluorocoumarins afford benzothiazoles as a result of cleavage of the pyrone cycle, 2-methyl-3-ethoxycarbonyl-5,6,7,8-tetrafluorochromone undergoes acidic cleavage to 2-(2-hydroxy-3,4,5,6-tetrafluorophenyl)benzothiazole. S-Substituted coumarins in alkaline media suffer decomposition to acetophenone. In acidic media 3-iminoacetyl-4-hydroxy-5,6,8-trifluoro-7-(2-aminophenylthio)coumarin affords 2-methyl-5,6,8-trifluoro-7-(2-aminophenylthio)chromone. In condensation of 4-hydroxy-5,6,8-trifluoro-7-(2-aminophenylthio)coumarin in the presence of NaH was isolated 4-hydroxy-5,6-difluoro-2H-pyrano[6,5-a]phenothiazin2-one.     

Synthesis of 2-(6-Methoxy-2-Quinolyl) Chromone Derivatives

In the continuous investigation of structure and activity correlation of flavonoids, several 2′-hydroxy-2-6(6-methoxy-2-quinolyl)chromone derivatives and their intermediates 2′-hydroxy-2-(6-methoxy-2-quinolyl)acrylophenones were synthesized by the condensation of 6-methoxy-2-quinoline aldehyde with appropriate 2-hydroxoxy-acetophenones in the presence of alcoholic potassium hydroxide, and then oxidized by selenium dioxide.     

Synthesis of 2-hydroxy-2-phenylethylamino derivatives as potential α-adrenergic blocking agents

The synthesis of N,N'-bis[6-(2-hydroxy-2-phenylethylamino)hexyl] cystamines 4 , and N-(2-hydroxy-2-phenylethyl)-1,6-hexanediamines 6 are described. Compounds 4 were obtained by condensation of the requisite epoxide 2 with 3-(6-aminohexyl)-1,3-thiazolidine followed by dimerization with opening of the thiazolidine ring. A similar method was used for the preparation of compounds 6. In order to prepare 4j (N,N'-bis{6-[2-hydroxy-2(3,4-dihydroxyphenyl)ethylamino]hexyl}cystamine), several procedures were tested; the method of choice involved the use of 3,4-dihydroxybenzaldehyde with both hydroxy groups protected as methoxymethyl ethers.     

Facile Synthesis of 5-Hydroxy-2-（2-phenylethyl）chromone

5-Hydroxy-2-(2-phenylethyl)chromone(1) was synthesized from 2,6-dihydroxyacetophenone(7) obtained via four-steps resorcinol-reacting with phenylpropionic acid,the procedures involved are Baker-Venkataraman rearrangement and cyclization which are easy to conduct,the overall yield is 32%.     

Reactions of 5,6,7,8-Tetrafluoro-4-hydroxy-2H-chromen-2-ones with methylamine

5,6,7,8-Tetrafluoro-4-hydroxy-2H-chromen-2-one reacts with methylamine to give methylammonium 5,6,7,8-tetrafluoro-2-oxo-2H-chromen-4-olate, regardless of the solvent. The reaction of 3-acetyl-5,6,7,8-tetrafluoro-4-hydroxy-2H-chromen-2-one with the same amine in ethanol or acetonitrile leads to the formation of methylammonium 3-acetyl-5,6,7,8-tetrafluoro-2-oxo-2H-chromen-4-olate, while in dimethyl sulfoxide 5,6,8-trifluoro-7-methylamino-3-(1-methylaminoethylidene)-3,4-dihydro-2H-chromene-2,4-dione is formed. The latter is also formed in the reaction of 5,6,7,8-tetrafluoro-4-hydroxy-3-(1-iminoethyl)-2H-chromen-2-one with methylamine in DMSO, whereas in ethanol and acetonitrile 5,6,7,8-tetrafluoro-3-(1-methylaminoethylidene)-3,4-dihydro-2H-chromene-2,4-dione is obtained. 5,6,7,8-Tetrafluoro-3-(1-methylaminoethylidene)-3,4-dihydro-2H-chromene-2,4-dione reacts with methylamine, yielding 7-mono-or 5,7-bis(methylamino)-substituted derivatives.     

Synthesis of 3-Hydroxy-6-Methyl- and 3-Hydroxy-2-(2-phenylethyl)pyridines and Their Sulfur-Containing Amino and Hydroxymethyl Derivatives

The aminomethylation of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines by secondary amines has been investigated. It was shown that like 2-alkyl-3-hydroxypyridine aminomethylation is directed primarily to position 6 and then 4 of the pyridine ring. On heating the aminomethyl derivatives of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines with acetic anhydride the corresponding acetoxy derivatives were obtained, which were converted on heating with hydrochloric or hydrobromic acids into hydroxy and bromomethyl derivatives. Isothioureidomethyl and benzimidazolylthiomethyl derivatives were synthesized by heating the bromomethyl-substituted derivative with thiourea or with 2-mercaptobenzimidazole. The structures of compounds were confirmed by data of ¹H NMR spectra. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1189–1194, August, 2005.     

Tetrahydroquinazoline-substituted chromones from Diels–Alder reaction of (E)-2-styrylchromones and pyrimidine ortho-quinodimethane

The Diels–Alder reaction of (E)-2-styrylchromones with a pyrimidine ortho-quinodimethane is reported for the first time. These cycloaddition reactions afford mixtures of two regioisomeric tetrahydroquinazoline-substituted chromones in moderate to excellent global yields. Irrespective of the substituents on the 2-styrylchromones, the 2-(7-aryl-4-methoxy-2-methyl-5,6,7,8-tetrahydroquinazolin-6-yl)chromone derivatives are always the major isomers.     

New sesquiterpenes from Ferula ferulaeoides (Steud.) Korovin. VI. Isolation and identification of three new dihydrofuro[2,3-b]chromones

Three novel 2-prenyl-dihydrofurochromone-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[2,3-b]chromone, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E),7-pentenyl]-furo[2,3-b]chromone, and 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E),7-pentenyl]-furo[2,3-b]chromone, were isolated from the roots of Ferula ferulaeoides. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these 2-prenyl-dihydrofurochromone-type sesquiterpenoids is proposed based on their structures.     

Chemical constituents of malagasy liverworts, part V: prenyl bibenzyls and clerodane diterpenoids with nitric oxide inhibitory activity from Radula appressa and Thysananthus spathulistipus

3Beta,4beta:15,16-diepoxy-13(16),14-clerodadiene (1) and a new clerodane diterpenoid designated thysaspathone (2) were isolated from the liverwort Thysananthus spathulistipus, while Radula appressa produced radulannin A (3), radulannin L (4), 2-geranyl-3,5-dihydroxybibenzyl (5), 2(S)-2-methyl-2-(4-methyl-3-pentenyl)-7-hydroxy-5-(2-phenylethyl) chromene (o-cannabichromene) (6), 6-hydroxy-4-(2-phenylethyl) benzofuran (7), and o-cannabicyclol (8). All of the isolated compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the greatest inhibition was attributed to compound 5, with an IC50 value of 4.5 microM.     

Synthesis and crystal structure of <Emphasis Type="Italic">N</Emphasis>(12)-(2-hydroxy-2-phenylethyl)cytisine

Diastereomers of N(12)-(2-hydroxy-2-phenylethyl)cytisine were synthesized by reduction of N(12)-(2-oxo-2-phenylethyl)cytisine by Yamamoto reagent. Their structures were solved using x-ray structure analysis.     

Reactions of 2(3)-ethoxycarbonyl-5,6,7,8-tetrafluorochromones with methylamine

2-Ethoxycarbonyl-5,6,7,8-tetrafluorochromone reacts with methylamine differently, depending on the solvent nature and the amount of the amine: in DMSO and MeCN, the fluorine atom at the C(7) atom is initially replaced and then the C(2) and/or C(9) are attacked, while in ethanol, the reaction involves the C(2) atom with opening of the pyrone ring. The reaction of 3-ethoxycarbonyl-5,6,7,8-tetrafluoro-2-methylchromone with methylamine results, regardless of the solvent, in opening of the chromone ring and the formation of intermediate ethyl 3-(3,4,5,6-tetrafluoro-2-hydroxyphenyl)-2-(1-methylamino)ethylidene-3-oxopropionate, which undergoes intramolecular cyclization to give 5,6,7,8-tetrafluoro-3-(1-methyl-amino)ethylidene-3,4-dihydro-2H-benzopyran-2,4-dione. Dedicated to Academician N. S. Zefirov on the occasion of his 70th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2093–2098, September, 2005.     

Synthesis and spectral analysis of (±)-cis-N-[1-(2-hydroxy-2-phenyl-ethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide and (±)-cis-N-[1-(2-hydroxy-1-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide

Treatment of (±)-cis-N-(3-methyl-4-piperidyl)-N-phenylpropanamide (2) with styrene oxide (1) yielded a mixture of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (3) and (±)-cis-N-[1-(2-hydroxy-1-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (4) . The structure of compound 3 was confirmed by an unambiguous synthesis via (±)-cis-N-[1-(2-oxo-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (6) . The proton and carbon-13 resonances of compounds 3 and 4 were assigned with the aid of two-dimensional heteronuclear correlation experiments.     

Antiangiogenic polyketides from Peperomia dindygulensis Miq

Two new polyketides: 2Z-(heptadec-12-enyl)-4-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (1) and 2-(heptadec-12-enyl)-5-hydroxy-5,6,7,8-tetrahydrochromen- 4-one (2), together with eleven known compounds: 4-hydroxy-2-[(3,4-methylenedioxy- phenyl)tridecanoyl] cyclohexane-1,3-dione (3), oleiferinone (4), 4-hydroxy-2-[(3,4- methylenedioxyphenyl)undecanoyl]cyclohexane-1,3-dione (5), 4-hydroxy-2-[(11-phenyl- undecanoyl)cyclohexane-1,3-dione (6), proctorione C (7), surinone C (8), 5-hydroxy- 7,8,4'-trimethoxyflavone (9), 5-hydroxy-7,8,3',4'-tetramethoxyflavone (10), 5-hydroxy- 7,3',4'-trimethoxyflavone (11), 5,8-dihydroxy-7,3',4'-trimethoxyflavone (12) and cepharanone B (13) were isolated from the whole plant of Peperomia dindygulensis Miq. Their structures were elucidated by spectroscopic methods, including 2D-NMR techniques. Compounds 2, 3, 5 and 8 inhibited human umbilical vein endothelial cell (HUVEC) proliferation and compounds 5 and 8 sharply suppressed HUVEC tube formation.     

Enantioselective synthesis of (+)-(S)-7,8-dihydrokavain and (4R,6R)-4-hydroxy-6-(2-phenylethyl)tetrahydro-2H-pyran-2-one, lactone analog of compactin and mevinolin

A simple and efficient asymmetric synthesis was performed of (+)-(S)-7,8-dihydrokanian and (4R,6R)-4-hydroxy-6-(2-phenylethyl)tetrahydro-2H-pyran-2-one involving Keck allylation in the key stage of building up the carbon scaffold of the target molecules.     

Reactions of 2-ethoxycarbonyl(carboxy)-5,6,7,8-tetrafluorochromones with N-nucleophiles

The direction of reactions of 2-ethoxycarbonyl-5,6,7,8-tetrafluoro- and 2-carboxy-5,6,7,8-tetrafluorochromones with ammonia, methylamine, hexylamine, and aniline depends on the inductive effect of the substituent at position C-2 of the chromone and on the basicity of the amine. Nucleophilic aromatic substitution of a fluorine atom takes place in the interaction of 2-ethoxycarbonyl-5,6,7,8-tetrafluorochromone with secondary amines (morpholine,N-methylpiperazine) and ethylenediamine.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 904–907, May, 1994.     

Polyfluorinated heterocyclic compounds

The treatment of 2-phenyl-4-carbomethoxy-6,7,8,9-tetrafluorobenz[f]oxazepin-1,3 (I), 3-benzamido-5,6,7,8-tetrafluorocoumarin (V), and α-benzamido-β-(2-hydroxy-3,4,5,6-tetrafluorophenyl)-acrylic acid (III) with a mixture of glacial acetic acid and a mineral acid gave (IV), the π-complex of 3-hydroxy-5,6,7,8-tetrafluorocoumarin (VII) and benzoic acid. Treatment of (IV) with acetic anhydride gave 3-acetoxy-5,6,7,8-tetrafluorocoumarin (VI) and benzoic acid. Treatment with diazomethane gave 3-methoxy-5,6,7,8-tetrafluorocoumarin (VIII) and methyl benzoate. IV was also obtained from an equimolar mixture of its components. A mechanism for the formation of IV from I is proposed.     

Reactions of N-(2,2-Dichloro-2-phenylethylidene)arenesulfonamides with Aromatic and Heterocyclic Compounds

Benzene, toluene, and 2-chlorothiophene regioselectively react with N-(2,2-dichloro-2-phenyl- ethylidene)arenesulfonamides in the presence of oleum to give N-[1-aryl(or hetaryl)-2,2-dichloro-2-phenylethyl]arenesulfonamides. Analogous C-amidoalkylation products are formed by the action of N-(2,2-dichloro- 1-hydroxy-2-phenylethyl)- and N-(1-arylsulfonylamino-2,2-dichloro-2-phenylethyl)arenesulfonamides on toluene and 2-chlorothiophene in concentrated sulfuric acid.