Über die Reaktion von 3,5-Diacetyl-2,6-dimethyl-4H-pyran-4-on mit Natriumalkanolaten

On the Reaction of 3,5-Diacetyl-2,6-dimethyl-4H-pyran-4-one with Sodium Alkoxides The reaction of 3,5-diacetyl-2,6-dimethyl-4H-pyran-4-one (10) with sodium methoxide or ethoxide leads to the formation of the 1-acetyl-2-hydroxy-4-methyl-6-alkoxybenzenes 11a and 11b .     

5个不同地区绞股蓝中挥发性成分的SPME-GC-MS分析

目的:建立固相微萃取-气相色谱质谱方法,对采自4省市5个地区药用植物绞股蓝的挥发性化学成分进行定性定量分析。方法:采用固相微萃取-气相色谱-质谱(SPME-GC-MS)联用技术对绞股蓝挥发性成分进行分析,利用峰面积归一化法测定各个成分的相对百分含量。结果:5个地区的绞股蓝中,总共分离出67个成分,主要含有醛类、酮类、烷烃类、烯烃类、芳香烃类、醇类和脂类。5个样品中共有成分6个,分别为:3,7-二甲基-1,6-辛二烯-3-醇、萘、α-紫罗酮、香叶基丙酮、β-紫罗酮和6,10,14-三甲基-2-十五烷酮。其中平利绞股蓝中含量最高的成分为3-辛酮(14.93%),宁陕鱼洞村绞股蓝中含量最高的为香叶基丙酮(10.8%),湖南麻姑仙境绞股蓝中含量最高的为3,7-二甲基-1,6-辛二烯-3-醇(22.4%),重庆缙云山和四川青城山绞股蓝中含量最高的均为安息香醛,含量分别为63.16%和38.52%。结论:5个地区绞股蓝中挥发性成分差异性很大。     

Inhibitors of folate biosynthesis. 1. Inhibition of dihydroneopterin aldolase by pteridine derivatives.

2-Amino-6-carboxamido-7,8-dihydropteridin-4-one and 2-amino-6-hydroxymethyl-7,7-dimethyl-7,8-dihydropteridin-4-one have been shown to be good inhibitors of Escherichia coli dihydroneopterin aldolase, an early enzyme of de novo folate biosynthesis.     

A sustainable approach for synthesizing Diels-Alder adducts using microwave reactor

Diels-Alder reactions of 1,3-butadiene, 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene (dienes) with maleic anhydride, maleic acid, 1,4-benzoquinone, 2-cyclopenten-1-one and 2-cyclohexen-1-one (dienophiles) in the presence of 3-methyl-1-octylimidazolium tetrachloroaluminate ionic liquid, namely [C₈MIM] AlCl₄ in conjunction with a variety of solid supports were found to be efficient to afford good to excellent yields both in conventional method at 75 °C and microwave irradiation method at 60 °C. This work-up procedure has many advantages, which include quick reaction, high yields, minimal wastes, recoverability and reusability of ionic liquids and operational simplicity.     

Kondensationen mit Hydrazin-N,N′-dicarbonsäurediamidin, 21. Mitt. β-Ketocarbonsäureester als Reaktionspartner

Condensations with 1,2-Hydrazinedicarboxamidine, XXI: β-Ketocarboxylic Esters as Reactants In preceding investigations it was assumed that the guanidinoaminopyrimidine structure is a common intermediate in the formation of hydrazo- and the triazolopyrimidines from 1,2-hydrazinedicarboxamidine (1) . This postulate is now supported by the isolation of 2-guanidinoamino-6-methyl-1,4-dihydropyrimidin-4-one (3) formed by the reaction of 1 with ethyl acetoacetate (2) and by the conversion of 3 into 2-amino-7-methyl-5,8-dihydro-s-triazolo[1,5-a]pyrimidin-5-one (8a) . In the course of this conversion 6,6′-dimethyl-2,2′hydrazo-1,4-dihydropyrimidin-4-one (4) is formed from 3 .     

Photo- und strahlenchemische Studien, 46. Mitt. Zur Photochemie des Isopropylaminophenazons im kristallinen Zustand und in wäßriger Lösung

Photochemical Studies, XLVI: Photochemistry of Isopropylaminophenazone in the Solid State and in Aqueous Solution Photolysis of 4-(isopropylamino)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (isopropylaminophenazone) ( 1 ) in the solid state (A) or in aqueous solution (B) leads to: (A) N-isopropyl-N′-phenyloxamide, N′-acetyl-N′-methyl-N-(isopropylaminooxalyl)phenylhydrazine ( 2 ) and 2-(isopropylimino)-3-(methylimino)butyric acid anilide ( 3 ); (B) methyltartronic acid anilide isopropylamide ( 4 ), methyltartronic acid anilide methylamide ( 5 ), N-phenyl-N-(2-methylaminopropionyl)carbamic acid ( 6 ) and isopropylamine. The rearrangement of 1 to 3 is the first example of a solid state photoisomerisation in a 3-pyrazolin-5-one derivative.     

2-甲基-4-(2,6,6-三甲基-1-环己烯-1-基)-2-丁烯醛的合成

2,6,6-三甲基-1-环己烯-1-甲醛与(3-甲氧基-2-甲基烯丙基)膦酸二乙酯经Wittig-Homer缩合制得1-甲氧基-2-甲基-4-(2,6,6-三甲基-1-环己烯-1-基)-1,3-丁二烯,然后经酸催化水解得到维生素A的关键中间体2-甲基-4-(2,6,6-三甲基-1-环己烯-1-基)-2-丁烯醛,总收率约47%.     

Two new monoterpenoid glycosides from Mentha spicata L.

Two new monoterpenoid glycosides, spicatoside A and spicatoside B, were isolated from the whole herbs of Mentha spicata L. which have anti-inflammatory and hemostatic activities. Their structures have been determined on the basis of spectral and chemical analysis. They are (+)-5-[1-(g -D-glucopyranosyloxymethyl)ethenyl]-2-methyl-2-cyclohexen-1-one (1), and (m )-5-{[2-( g -D-glucopyranosyloxy)-1-hydroxy-1-methyl]ethyl}-2-methyl-2-cyclohexen-1-one (2).     

Pyroglutamic Acid in Drug Synthesis,Part 1 A Method for the Synthesis of Enantiomerically Pure 4-Alkyl-4-arylpyroglutamic Acids

Synthesis of the title compounds is described, starting from alkylation of the pyroglutaminol-acetal 4a ^[1] at the α-lactam position C-6 with methyl iodide. Subsequent addition of 2-cyclohexen-1-one led to diastereoselective formation of the 1,2-aldol addition product 7b/7c , which after dehydratization was aromatized with DDQ to yield the 6-methyl-6-phenyl derivative 7h. Acetal cleavage and Jones oxidation yielded 4,4-disubstituted, enantiomerically pure pyroglutamic acid 3b. X-ray analysis confirmed the assignment of the configuration of the newly created chiral centre.     

7α,17α-二甲基-17β-羟基雄甾-4-烯-3酮的若干A环骈杂环衍生物的合成

将7α-甲基引进甲基睾丸素后,经甲酰化反应制得2-羟次甲基衍生物(Ⅳ),再先后转变为单肟(Ⅴ)、双肟(Ⅵ),环合得70,17α-二甲基-17β-羟基-雄甾-4-烯骈[2,3-c]呋咱(Ⅶ)。也可使(Ⅳ)与水合肼或盐酸羟胺作用,分别制得相应的雄甾-4-烯骈[3,2-c]吡唑(Ⅷ)及雄甾2,4-二烯骈[2,3-d]异(口恶)唑(Ⅸ)。在酸性反应条件下合成(Ⅸ)时,还分离出它的重排脱水产物7α,17α,17β-三甲基雄甾-2,4,13-三烯骈[2,3-d]异(口恶)唑(Ⅹ)。     

Synthesis of 4-(2,4-dioxo-5-pyrimidyl)-1,4-dihydropyridine derivatives

Hantzsch synthesis of 5-formyluracil (1), methyl acetoacetate (2) and methyl 3-aminocrotonate (3) gave 2,6-dimethyl-4-(2,4-dioxo-5-pyrimidyl)-1, 4-dihydropyridine-3, 5-dicarboxylic acid dimethylester (4a) in 54.6% yield. As the same procedure, 1,3-dimethyl-5-formyl-uracil (6) gave 2,6-dimethyl-4-(1,3-dimethyl-2,4-dioxo-5-pyrimidyl)-1, 4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (7a) in 52.2% yield.4a was methylated to afford7a also in 52% yield.     

Acetylenchemie, 3. Mitt. Ein einfacher Zugang zum Flindersin via Phasen-Transfer-Reaktion

Acetylene Chemistry, III: A Simple Approach to Flindersine by Phase-Transfer Reaction Reaction of 4-hydroxyquinolin-2-one (4) with 3-chloro-3-methylbut-1-yne by phase-transfer catalysis affords flindersine (3) and 2,3-dihydro-3,3-dimethyl-2-methylenefuro[3,2-c]quinolin-4-one (5) , whereas indolin-2-one (4g) yields N-(1′,1′-dimethylprop-2-yn-1-yl)indolin-2-one (19) . The reaction mechanism is discussed and studied by varying the reaction conditions.     

Metabolic fate of menthofuran in rats. Novel oxidative pathways.

Metabolic fate of menthofuran (II) in rats was investigated. Menthofuran (II) was administered orally (200 mg/kg of the body weight/day) to rats for 3 days. The following metabolites were isolated from the urine of these animals: p-cresol (VI), 5-methyl-2-cyclohexen-1-one (VII), 3-methylcyclohexanone (VIII), 3-methylcyclohexanol (IX), 4-hydroxy-4-methyl-2-cyclohexen-1-one (V), geranic acid (XI), neronic acid (XII), benzoic acid (XIII), and 2-[2'-keto-4'-methylcyclohexyl]propionic acid (X). Incubation of menthofuran (II) with phenobarbital-induced rat liver microsomes in the presence of NADPH and oxygen resulted in the formation of a metabolite tentatively identified as 2-Z-(2'-keto-4'-methylcyclohexylidene)propanal (III; alpha,beta-unsaturated-gamma-keto-aldehyde). The structure assigned was further supported by trapping this metabolite (III) as a cinnoline derivative. Phenobarbital-induced rat liver microsomes also converted 4-methyl-2-cyclohexenone (IV) to 4-hydroxy-4-methyl-2-cyclohexenone (V) and p-cresol (VI) in the presence of NADPH and oxygen. On the basis of both in vivo and in vitro studies, a possible mechanism for the formation of p-cresol from menthofuran has been proposed.     

Identification of in vitro rat metabolites of 1-phenylcyclohexene

In vitro metabolites of 1-phenylcyclohexene produced by the 10,000g supernatant fraction from rat liver homogenates were identified by a combination of spectrometric, chromatographic, and synthetic techniques. Initial oxidation occurred in the 3-position of 1-phenylcyclohexene to yield 1-phenyl-1-cyclohexen-3-one and 1-phenyl-1-cyclohexen-3-ol. Further allylic oxidation at the 6-position occurred to form 1-phenyl-6-hydroxy-1-cyclohexen-3-one and 1-phenyl-1-cyclohexene-3,6-diol. Trans-1-phenyl-1-cyclohexene-3,4-diol was also found and may have resulted from hydroxylation of 1-phenyl-1-cyclohexen-3-one alpha to the carbonyl to yield 4-hydroxy-1-phenyl-1-cyclohexen-3-one (not isolated) followed by carbonyl reduction. Oxidation of the double bond also occurred to give the cis and trans isomers of 1-phenylcyclohexane-1,2-diol as well as a compound postulated to be 1-phenylcyclohexane-1,2,3-triol.     

Sesquiterpenoids from Ferula fukanensis and their inhibitory effects on nitric oxide production

Six sesquiterpene derivatives, 2,3-dihydro-7-methoxy-2S*, 3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (1) and 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (2), nerolidol (3), 1-(2,4-dihydroxyphenyl)-3,7,11-trimethyl-3-ninyl-6(E),10-dodecadien-1-one (4), 1-(2,4-dihydroxyphenyl)-3,7-dimethyl-3-vinyl-8-(4-methyl-2-furyl)-6(E)-octen-1-one (5) and dshamirone (6) were isolated from an 80% aqueous methanol extract of the roots of Ferula fukanensis. The sesquiterpenoids inhibited nitric oxide (NO) production and inducible NO synthase gene expression by a murine macrophage-like cell line (RAW 264.7) [1], which was activated by lipopolysaccharide and recombinant mouse interferon-.     

Two new flavan-4-ol glycosides from Abacopteris penangiana

Two new flavan-4-ol glycosides, (2R,4S)-6,8-dimethyl-7-hydroxy-4′-methoxy-4,2″-oxidoflavan-5-O-β-d-6″-O-acetyl-glucopyranoside (1) and (2R,4S)-5,7-O-β-d-di-glucopyranosyloxy-4′-methoxy-6,8-dimethyl-4,2″-oxidoflavane (2), were isolated from the rhizomes of Abacopteris penangiana. Their structures were elucidated by spectroscopic methods. Compounds 1 and 2 showed significant anticancer activities against HeLa and L929 cell lines in vitro.     

Cellular Effects of Some Metabolic Oxidation Products Pertinent to 4-Ethoxyaniline

Abstract: The toxicity of some metabolic products pertinent to 4-ethoxyaniline in isolated hepatocytes were investigated. The compounds investigated were 4-ethoxynitrosobenzene (1), 4-ethoxy-4′-nitrosodiphenylamine (2), 3,6-bis(4-ethoxy-phenylimino)-4-ethoxy-1,4-cyclohexadienylamine (3), 4-(4-ethoxyphenylimino)-2,3-dimethyl-2,5-cyclohexadiene-1-one (4) and 4-(4-ethoxyphenylimino)-2,6-dimethyl-2,5-cyclohexadiene-1-one (5). Of these, 1, 2 and 3 are oxidation products of 4-ethoxyaniline. Compounds 4 and 5 are dimethyl analogues of previously investigated oxidation product 4-(4-ethoxyphenyl-imino(-2,5-cyclohexadiene-1-one (NEPBQI). Among the investigated compounds, 1 and 2 were the most toxic towards isolated hepatocytes. In hepatocytes treated with compounds 1, 2 and 4, loss of cell viability was also accompanied by surface bleb formation. All compounds except 3 reacted with GSH resulting in depletion of cellular GSH. No formation of GSSG was observed, however. Thus, the GSH depletion was apparently due to conjugate formation rather than oxidation. No superoxide dismutase inhibitable reduction of acetylated cytochrome c was observed, thus none of the compounds undergoes measurable redox cycling.     

Cellular effects of some metabolic oxidation products pertinent to 4-ethoxyaniline.

The toxicity of some metabolic products pertinent to 4-ethoxyaniline in isolated hepatocytes were investigated. The compounds investigated were 4-ethoxynitrosobenzene (1), 4-ethoxy-4'-nitrosodiphenylamine (2), 3,6-bis(4-ethoxy-phenylimino)-4-ethoxy-1,4-cyclohexadienylamine (3), 4-(4-ethoxyphenylimino)-2,3-dimethyl-2,5-cyclohexadiene-1-one (4) and 4-(4-ethoxyphenylimino)-2,6-dimethyl-2,5-cyclohexadiene-1-one (5). Of these, 1, 2 and 3 are oxidation products of 4-ethoxyaniline. Compounds 4 and 5 are dimethyl analogues of previously investigated oxidation product 4-(4-ethoxyphenylimino(-2,5-cyclohexadiene-1-one (NEPBQI). Among the investigated compounds, 1 and 2 were the most toxic towards isolated hepatocytes. In hepatocytes treated with compounds 1, 2 and 4, loss of cell viability was also accompanied by surface bleb formation. All compounds except 3 reacted with GSH resulting in depletion of cellular GSH. No formation of GSSG was observed, however. Thus, the GSH depletion was apparently due to conjugate formation rather than oxidation. No superoxide dismutase inhibitable reduction of acetylated cytochrome c was observed, thus none of the compounds undergoes measurable redox cycling.     

Entzündungshemmende Wirkstoffe, 10. Mitt.1). 1-(4-Chlorphenyl)-2-pyrazolin-5-on-Derivate

Antiinflammatory Agents, X: 1-(4-Chlorophenyl)-2-pyrazolin-5-one Derivatives Aminomethynylation of 1-(4-chlorophenyl)-3-methyl-2-pyrazolin-5-one ( 2 ) initiated by s-triazine ( 1 ) yields 4-aminomethylene-1-(4-chlorophenyl)-3-methyl-2-pyrazolin-5-one ( 4 ). This, in turn, may form the C-rubazonic acid 5 or, in the presence of secondary amines 6 , the dehydro-C-Mannich bases 7 .     

Uptake and Biotransformation of 6,7-Dimethylquinoline and 6,8-Dimethylquinoline by Rainbow Trout (Salmo Gairdneri)

1. 6,7-Dimethylquinoline (6,7-DMQ) is readily taken up by rainbow trout and bioconcentrated in tissue after exposure to ca 1?mg/1 for 7.5?h. Mean bioconcentration factors (from water) were 21, 18, 6 and 14 for bile, liver, muscle and carcass respectively. Mean tissue concentrations after 69-96?h depuration were ND, ND, 0.54 and 0.48 μg/g for bile, liver, muscle and carcass respectively.

2. Major metabolites, following exposure to 6,7-DMQ, were conjugates (glucuronide or sulphate) of 7-hydroxymethyl-6-methylquinoline and 6-hydroxymethyl-7-methylquinoline. Mean concentration of metabolites in the bile were 500μg/g after 7.5?h exposure to ca 1?mg/1 and 1367 μg/g after 9.5?h exposure to ca 1?mg/1 and 69?h depuration.

3. 6,8-Dimethylquinoline (6,8-DMQ) is also readily bioconcentrated in fish tissue after exposure to ca 1?mg/1. Mean bioconcentration factors (from water) were 23, 20, 13 and 25 for bile, liver, muscle and carcass respectively. Mean tissue concentrations after 7?h exposure to ca 1?mg/1 and 63?h depuration were 4.0,0.67,0.49, and 3.2 μg/g respectively for bile, liver, muscle and carcass.

4. Major metabolites, following exposure to 6,8-DMQ were conjugates (glucuronide or sulphate) of 6,8-dimethyl-5-hydroxyquinoline, 6,8-dimethyl-7-hydroxyquinoline. 6,8-dimethyl-3-hydroxyquinoline and 6-hydroxymethyl-8-methylquinoline. Mean concentration of metabolites in the bile were 1278 μg/g after exposure to ca 1?mg/1 for 8?h and 1031 μg after exposure to ca 1?mg/1 for 7h and 63?h depuration.