Preparation of 5-Cyano-4,6-dimethyl-2H-pyran-2-one and 3-Cyano-5-methoxy-4-methyl-5H-furan-2-one via a One-Pot,Domino-Knoevenagel Process

5-Cyano-4,6-dimethyl-2H-pyran-2-one (1) has been prepared via a simple one-pot domino-Knoevenagel reaction starting from ethyl acetoacetate (2) and cyanoacetone (3). Similarly, a new racemic 3-cyano-5-methoxy-4-methyl-5H-furan-2-one (7) has been prepared from 1,1-dimethoxyacetone (6) and cyanoacetic acid (4). The new alkylidene derivatives (Z/E)-ethyl-4-cyano-3-methylbut-3-enoate (5), (Z/E)-ethyl 5-amino-4-cyano-3-methyl-5-oxopent-3-enoate (9), and (2,2-dimethoxy-1-methylethylidene)malononitrile (11) have been prepared via the Knoevenagel reactions. The easy access to these new compounds in good yields shows that ammonium acetate/acetic acid–catalyzed Knoevenagel reactions and domino-Knoevenagel reactions have a broad scope of application.     

Synthesis and spectral studies of pyranone derivative and its Cu(II), Co(II), Ni(II) and Zn(II) complexes

Under the thermolysis condition, 5-phenyl-2,3-dihydro-2,3-furandione (IV) in inert aprotic solvents as p-xylene at 130–140°C yields 3-benzoyl-4-hydroxy-6-phenyl-2H-pyran-2-one (VI) via phenyl ketene (V). The compound (VI) was converted into the corresponding 3-benzoyl-4-hydroxy-6-phenylpyridin-2(1H)-one (VII), and 3-benzoyl-2-oxo-6-phenyl-2H-pyran-4-yl acetate (VIII), by its reactions with ammonium hydroxyde, and acetic anhydride, respectively. On the other hand, a series of new various metal complexes (IX-XIa, XIb) of VI was synthesized. The results suggest that the compound VI as bidentate ligand indicate a binuclear structure for the Cu(II) complex with square-planar geometry. The Ni(II) and Zn(II) complexes are of tetrahedral and the Co(II) complex is also octahedral geometry with water molecules at the axial positions. The structures of compounds and complexes were characterized on the basis of elemental analysis, Mass, IR, ¹H, and ¹³C NMR spectra. The text was submitted by the authors in English.     

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.     

Previously undescribed benzoxepins with bioactivities against inducible pro-inflammatory cyclooxygenase and lipoxygenase from Rhizophora annamalayana Kathir

Two unprecedented benzoxepins were obtained from the ethyl acetate fraction of the leaves of Rhizophora annamalayana Kathir, and characterized as 4-(11-(hydroxymethyl)-10-methylpentan-2-yl)-4, 5-dihydrobenzo[c]oxepin-1(3H)-one (1) and (E)-methyl-14-hydroxy-4-(11-(5-hydroxy-1-oxo-3,4,5-tetrahydrobenzo[c]oxepin-4-yl)ethyl)-10-methylhept-11-enoate (2). The benzoxepin 2 exhibited greater 1, 1-diphenyl-2-picrylhydrazyl and 2, 2′-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid diammonium radical scavenging assays (IC₅₀ 0.68 and 0.84 mg/mL, respectively) than those recorded with 1 (IC₅₀ 0.70 and 0.89 mg/mL, respectively). The tetrahydrobenzo[c]oxepin analogue (2) exhibited significantly great cyclooxygenase-2 and 5-lipoxygenase inhibitory properties (IC₅₀ 0.87 and 0.94 mg/mL, respectively), while compared with its dihydrobenzo[c]oxepin-1(3H)-one isoform (1) (IC₅₀ 1.16 and 1.64 mg/mL, respectively). The dihydrobenzo[c]oxepin-1(3H)-one isoform (2) exhibited significantly greater selectivity index (~2) than synthetic ibuprofen (0.44) (p < 0.05), which attributed the higher anti-inflammatory selectivity of the former against inducible pro-inflammatory cyclooxygenase-2 than its constitutive isoform (cyclooxygenase-1). No significant difference in 5-lipoxygenase (5-LOX) inhibitory activities were apparent between compound 2 (IC₅₀ 0.94 mg/mL) and synthetic ibuprofen (IC₅₀ 0.93 mg/mL).     

Condensation reactions of a comenaldehyde derivative

Condensation reactions of comenaldehyde methyl ether (I) with malonic acid, ethyl cyanoacetate, and cyanoacetamide to give β-(5-methoxy-4H-pyran-4-on-2-yl)acrylic acid (II), ethyl 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenoate (III), and 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenamide (IV), respectively, are described. Ultraviolet absorption spectra for 2-hydroxymethyl-5-methoxy-4H-pyran-4-one, I and II are presented.     

Products from furans. VI. Synthesis of dihydro-2-disubstituted-2H-pyran-3(4H)-ones,tetrahydro-3-(aminomethyl)-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3-ol derivatives and 6-(p-methoxyphenyl -6-methyl-7-oxa-1,3-diazaspiro[4,5]decane-2,4-dione

Hydrogenolysis of 5,6-dihydro-6-(p-methoxyphenyl)-6-methyl-5-oxo-2H-pyran-2-yl ethyl carbonate yielded dihydro-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3(4H)-one, 3 . Subsequently cyanohydrin 4 , derived from 3 , on reduction afforded 3-(aminomethyl)tetrahydro-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3-ol, 5 . The synthesis of N-dimethyl,N-isopropyl,N-imidazolyl as well as N-oxazolinyl derivatives of 5 is presented. The synthesis of 6-(p-methoxyphenyl)-6-methyl-7-oxa-1,3-diazaspiro[4,5]decane-2,4-dione 10 , a spiro hydantoin prepared from ketone 3 is also reported.     

Preparative separation of six coumarins from the pummelo (Citrus maxima (Burm.) Merr. Cv. Shatian Yu) peel by high-speed countercurrent chromatography

In this work, six coumarins, including two new ones, 8-(3-hydroxy-2,2-dimethylpropyl)-7-methoxy-2H-chromen-2-one (2) and 5-[(7′,8′-dihydroxy-3′,8′-dimethyl-2-nonadienyl)oxy] psoralen (4), as well as four known ones, 5-[(6′,7′-dihydroxy-3′,7′-dimethyl-2-octenyl) oxy] psoralen (1), marmin (3), epoxybergamottin (5), and aurapten (6) were successfully separated from the crude extract of pummelo (Citrus maxima (Burm.) Merr. Cv. Shatian Yu) peel by high-speed countercurrent chromatography in a single run with petroleum-ether–ethyl acetate–methanol–water (4:6:6:4, v/v). The structures of these six coumarins were elucidated by ESI-MS, extensive 1D and 2D NMR spectroscopy.     

Isolation,Structure, and Biological Activities of Long-Chain Catechols of Plectranthus sylvestris (Labiatae)

Antioxidant activity guided fractionation of extracts of the aerial parts of the title plant and HPLC separation yielded a series of oxygenated long-chain alkylcatechols. Their structures were inferred by spectroscopic methods and chemical transformations to be the novel 4-[(2S,4R,6S)-4-(acetyloxy)tetrahydro-6-pentyl-2H-pyran-2-yl]benzene-1,2diol ( 1a ), 4-[(2S,4R6S)-tetrahydro-4-hydroxy-6-pentyl-2H-pyran-2-yl]benzene-1,2-diol ( 1b ), 4-[(3S,5S)-5-(acetyloxy)-3-hydroxydecyl]benzene-1,2-diol (2a), 4-[(3S,5S)3-(acetyloxy)-5-hydroxydecyl]benzene-1,2-diol ( 2b ), (3S,13Z)-1-(3,4-dihydroxyphenyl)-3-hydroxydocos-13-en-5-one ( 3a ), (Z)-1-(3,4-dihydroxyphenyl)docos-13-en-5-one ( 4 ), besides the known l-(3,4-dihydroxyphenyl)icosan-5-one ( 5 ). The absolute configurations of the optically active compounds which are structurally related to the [n]-gingerols ( 6 ) and -diols ( 7 ) were established by the high-field ¹H-NMR application of Mosher's method. All compounds are in vitro potent antioxidants, inhibiting the Fe²⁺-catalysed autoxidation of linoleic acid in the same order of magnitude as the commercial antioxidant 2,6-di(tert-butyl)-4-methylphenol (BHT). The dose-dependent inhibitory effects on soybean-lipoxygenase are in the μmol range, that of the most effective compound ( 3a ) in the nmol range, hence being significantly more potent than the Known anti-inflammatory and analgesic drugs indomethacin and nordihydroguaiaretic acid.     

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.     

Über 1.4-Dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptane

Zusammenfassung 2.5-Dialkyl-3.4-dihydro-2H-pyran-2-aldehyde (1 c–1 f) setzen sich mit Acetamid und Essigsäureanhydrid zu 2,5-Dialky-3.4-dihydro-2H-pyran-2-methandioldiacetaten (2 c–2 f), N.N-[(2.5-Dialkyl-3.4-dihydro-2H-pyran-2-yl)-methylen]bisacetamiden (3 c–3 f) und zu 1.4-Dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptanen (6 c–6 f) um. Ausdem 3.4-Dihydro-2H-pyran-2-aldehyd (1 a) entsteht unter gleichen Bedingungen kein Oxabicycloheptan. Mit Methylharnstoff reagieren die genannten Pyranaldehyde zu Pyranylmethylenbismethylharnstoffen9 c–9 f.

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1.4-dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptanes

2.5-Dialkyl-3.4-dihydro-2H-pyran-2-carboxaldehydes (1 c to1 f) are transformed by acetamide and acetic anhydride to 2.5-dialkyl-3.4-dihydro-2H-pyran-2-methanediol diacetates (2 c to2 f), N.N-[(2.5-dialkyl-3.4-dihydro-2H-pyran-2-yl)-methylen] bisacetamides (3 c–3 f) and to 1.4-dialkyl-3-acetoxy-7-acetamido-2-oxabicyclo[2.2.1]heptanes (6 c–6 f). 3.4-dihydro-2H-pyran-2-carboxaldehyde (1 a) is not converted to an oxabicycloheptane under the same conditions. With methylurea the pyranaldehydes mentioned react to pyranylmethylenebismethylureas9 c–9 f.

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Herrn Prof. Dr.M. Pailer zum 60. Geburtstag gewidmet.     

Enantio and diastereoselective total synthesis of all four stereoisomers of germicidin N

Abstract

Germicidin N (3-ethyl-4-hydroxy-6-[(1S, 2?R)?2-hydroxy-1-methylpropyl]-2H-pyran-2-one, 1), a new α-pyrone from the extracts of a Streptomyces sp. derived from marine algae, has been synthesized for the first time as four possible diastereomers from chiral β-hydroxyester ((S)?6 and (R)?9) through the stereoselective alkylation, Claisen condensation followed by cyclization in a straightforward manner.     

Stereoselective ring closure of 6-[[(methylamino)carbonyl]oxy]-2H-pyran-3(6H)-ones. Formation of the 5H-pyrano[3,2-d]oxazole-2,6-dione ring system

The stereospecific formation of the 5H-pyrano[3,2-d]oxazole-2,6-dione ring system from 2,2-disubstituted-6-[[(methylamino)carbonyl]oxy]-2H-pyran-3(6H)-one via an enolization at C-5 is presented. The outcome of the same reaction in the case of 2-monosubstituted 2H-pyran-3(6H)-ones is also discussed.     

Synthese von einigen 2H-Pyran-2-on-Derivaten

The Synthesis of Some 2H-Pyran-2-one Derivatives Derivatives of 6-unsubstituted 2H-pyran-2-one have been synthesized by several different methods. The 4-chloro-2H-pyran-2-one ( 9 ) is the most important, since it serves as starting material for the synthesis of different 4-substituted 2H-pyran-2-ones (Scheme 2). Also described are simple transformations of cumalic-acid derivatives producing 5-(2,2-dichlorovinyl)-2H-pyran-2-one ( 23 ), 2-oxo-2H-pyran-2-carbonitrile ( 26 ), and 4,5-bis(trifluoromethyl)-2H-pyran-2-one ( 32 ) (Scheme 3 and 4).     

Condensed thiazoles,I: Synthesis of 5,7-disubstituted thiazolo[4,5-d]pyrimidines as possible anti-HIV,anticancer, and antimicrobial agents

Summary A convenient and simple synthesis of 5-mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo-[4,5-d]pyrimidin-7(6H-one(2) and its 5,7-dichloro (3), 5,7-diazido (4), 5,7-diamino (5), 5,7-dimerapto (6), 5,7-dimethylthio (7), and 6-methyl-5-methylthio (8) derivatives is described. The prepared compounds were screened for theirin vitro anti-HIV, anticancer, antibacterial and antifungal activities.

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Kondensierte Thiazole, 1. Mitt.: Synthese von 5,7-disubstituierten Thiazolo[4,5-d]pyrimidinen als potentielle anti-HIV, anticancerogene und antimikrobielle Verbindungen

Zusammenfassung Die Synthese von 5-Mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo[4,5-d-pyrimidin-7(6H)-on (2) und seiner 5,7-dichloro-(3), 5,7-diazido-(4), 5,7-dimanio-(5), 5,7-dimercapto-(6), 5,7-dimethylthio- (7) und 6-methyl-5-methylthio-Derivaten (8) wird beschrieben. Die hergestellten Verbindungen wurden auf ihrein vitro anti-HIV, anticancerogenen, antibakteriellen und antimykotischen Aktivitäten geprüft.

     

Chemical and biological studies on Bridelia ferruginea grown in Nigeria

Phytochemical investigation of the methanolic extract of dried leaves of Bridelia ferruginea led to the isolation and identification of fourteen compounds (1–14): compound 1 [mixture of palmitic, stearic and oleic acids], stearyl monoester of 2-O-β-?-glucosylglycerol (2), 6β-hydroxy-(20R)-24-ethylcholest-4-en-3-one (3a), 6β-hydroxy-(20R)-24-ethylcholest-4,22-dien-3-one (3b), lutein (4), vomifoliol (5), corilagin (6), kaempferide-3-O-β-?-glucoside (7), myricetin (8), isomericitrin (9), isoquercetin (10), myricitrin (11), quercitrin (12), rutin (13), and β-sitosterol glucoside (14). The total extract exhibited moderate activity towards CB2 receptor and 90% inhibition against leishmanial pathogen Trypanosoma brucei. Compound 4 exhibited 73% displacement in CB2 receptor with IC₅₀ 56.47 μM, and 93% inhibition towards T. brucei with IC₅₀ 4.16 μM. Compound 11 showed 99% inhibition towards Escherichia coli with IC₅₀ 1.123 μM.     

Two new benzolactones from the leaves of Nicotiana tabacum and their anti-tobacco mosaic virus activities

Two new benzolactones, 5-methyl-6-prenyl-isobenzofuran-1(3H)-one (1), 5-hydroxymethyl-6-prenyl-isobenzofuran-1(3H)-one (2), together with four known phenolic compounds (3–6), were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1–6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compounds 1–6 exhibited high anti-TMV activities with inhibition rates in the range of 16.9–26.2%, respectively.     

Polyketides with different post-modifications from desert endophytic fungus Paraphoma sp.

Three new polyketides 4,6,8-trihydroxy-5-methyl-3,4-dihydronaphthalen-1(2H)-one (1), 5,7-dihydroxy-3-(1-hydroxyethyl)-3,4-dimethylisobenzofuran-1(3H)-one (2) and 1-(4-hydroxy-6-methoxy-1,7-dimethyl-3-oxo-1,3-dihydroisobenzofuran-1-yl) ethyl acetate (3) together with seven known analogues (4–10) were isolated from desert endophytic fungus Paraphoma sp. The structures of these compounds were elucidated by analysis of NMR data. The absolute configuration of (1–3) was established on the basis of CD experiments. The possible biosynthetic pathway of compounds (1–10) was suggested, which implied that these secondary metabolites might be originated from polyketide biosynthesis with different post-modification reactions. Compounds 2, and 5–8 were evaluated for bioactivities against plant pathogen A. solani, whereas none of them displayed any biological effects. In addition, compounds 1, 2 and 5–10 were also tested for cytotoxic activities against three human cancer cell lines (HepG2 cells, MCF-7 cells and Hela cells) without biological effects.     

Studies on the constituents of the green alga <Emphasis Type="Italic">Ulva lactuca</Emphasis>

Phytochemical investigations on a marine green alga Ulva lactuca led to the isolation of two new compounds (E)-6-heptacosen-5-one (1) and (E)-6-octadecen-5-ol (2), along with four known compounds, (Z)-10-hexacosene (3), docosanoic acid (4), palmitic acid (5), and isofucosterol (6). Compounds 3 and 4 were isolated for the first time from this species. The structures of the compounds were deduced with the help of modern spectroscopic techniques.     

Antifungal activities and active ingredients of Melodinus suaveolens Champ. ex Benth.

Four Melodinus species with antifungal activity were found in survey of the floral resources, in Shiwan Mountain Natural Reserve, Guangxi Province, China. Crude methanolic extracts of the twigs and leaves of Melodinus suaveolens exhibited potent antifungal activities against the plant pathogenic fungi Colletotrichum musae, Colletotrichum graminicola, Colletotrichum gloeosporioides and Alternaria musae, and the ethyl acetate fraction inhibited these pathogens at rates of 85.37, 91.47, 72.77 and 89.87%, respectively (5 mg/mL). A new compound, (2R, 3S, 5S, 6R)-1-O-methyl- chiro-inositol was isolated from the ethyl acetate fraction, along with 15 known compounds. The antifungal activities of compounds (1–16) were evaluated for the first time. Compound (4) had potent antifungal activity against C. gloeosporioides, C. graminicola and A. musae.