A Novel Canthin-6-One Alkaloid Isolated from Cell Suspension Cultures of Brucea Javanica (L.) Merr

During investigation of cell suspension cultures of Brucea javanica (L.) Merr., the canthin-6-one alkaloid 5,11-dimethoxycanthin-6-one (1) was isolated. The structural determination is based on spectral analysis. Five other alkaloids, canthin-6-one-3-N-oxide (2), 11-hydroxycanthin-6-one (3), canthin-6-one (4), 5-methoxycanthin-6-one (5), and 11-methoxycanthin-6-one (6), were also identified.     

Regioselective dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones mediated by ceric ammonium nitrate

Ceric ammonium nitrate (CAN) has been explored for the regioselective oxidation of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs). Interestingly, we obtained ethyl 2,4-dioxo-6-phenyl-tetrahydropyrimidin-5-carboxylates as the major products during the oxidation of DHPMs by CAN/AcOH at 80 °C. The reaction afforded a mixture of products while employing CAN in organic solvents without additives. However, the regioselective dehydrogenated product, ethyl 6-methyl-4-aryl(alkyl)-pyrimidin-2(1H)-one-5-carboxylate was obtained by performing the reaction with NaHCO₃. The single crystal X-ray crystallography of ethyl 6-methyl-4-(2-phenyl)-pyrimidin-2(1H)-one-5-carboxylate revealed that the oxidized product existed in amidic form rather than aromatized enol form of pyrimidines. The efficiency of the present protocol enabled the synthesis of structurally diverse pyrimidines in moderate to good yields under milder reaction conditions.     

Reaction of ethyl 3-ethoxymethylene-2,4-dioxovalerate with monosubstituted hydrazines

Reactions of ethyl 3-ethoxymethylene-2,4-dioxovalerate (1) with phenyl- and methylhydrazines are described. While the reaction of 1 with phenylhydrazine gave a mixture of ethyl 4-acetyl-1-phenylpyrazole-5-carboxylate (4) and ethyl 5-methyl-1-phenylpyrazole-4-glyoxylate (5), 1 reacted with methylhydrazine to give ethyl 4-acetyl-1-methylpyrazole-3-carboxylate (14) as the sole product.     

Cyclocondensation of 2-hydrazinoperimidine with diethyl oxalate and ethyl pyruvate

Refluxing 2-hydrazinoperimidine (1) with excess amount of diethyl oxalate (2a) gave ethyl 1H-1,2,4-triazolo[4,3-a]perimidine-3-carboxylate (4a) in 84% yield. On the other hand, heating 1 with ethyl pyruvate (2b) in glacial acetic acid afforded 3-methyl-1,2,4-triazino[4,3-a]perimidin-4(1H)-one (6b) in 92% yield. Structures of the products were investigated by spectral and elemental analysis.     

Synthesis and application of ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate

Synthesis of ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate was achieved by diazotization of ethyl 2-amino-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate and coupling with selected N,N-dialkylanilines. The key intermediate ethyl 2-amino-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate was synthesized by the condensation of sodium salt of ethyl cyanoacetate with 2,3-dichloro-1,4-naphthoquinone. Ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate were applied on polyester fibers as disperse dyes and their dyeing properties were studied.     

Synthesis of fluoromethyl,difluoromethyl and trifluoromethyl analogues of pyrazosulfuron-ethyl as herbicides

Ethyl 1-fluoromethyl-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)pyrazole-4-carboxylate 1b , a new fluoromethyl analogue of the herbicide pyrazosulfuron-ethyl la, was prepared from ethyl 1-fluoromethylpyrazole-4-carboxylate 4b . The difluoromethyl and trifluoromethyl analogues 1c,d were also synthesized from ethyl pyrazole-4-carboxylate 2 via difluorocarbene reaction.     

A new selective preparation of ethyl 7-aminopteridine-6- carboxylate derivatives and related compound

A series of ethyl 7-amino-2,4-dioxopteridine-6-carboxylates 4 and ethyl 7-amino-4-oxo-2-thioxopteridine-6-carboxylates 5 , of interest biologically, has been prepared in one step from the reaction of such vicinal-diamines as 1,3-dialkyl-5,6-diaminouracils 2 or 1,3-dialkyl-5,6-diamino-2-thiouracils 3 with diethyl (E)-2,3-dicyanobutenedioate ( 1 ). Moreover, ethyl 3-amino[1,2,4]triazino[2,3-a]-1H-benzimidazole-2-carboxylate ( 11 ) was also obtained from the reaction between 1,2-diamino-1H-benzimidazole ( 10 ) and 1 . The structural studies of 4, 5 , and 11 prepared were carried out by nmr experiments in some details.     

Immobilization of Chiral Catalyst on Amorphous Al2O3 for the Selective Hydrogenation of Ethyl 1H-Indole-2-carboxylate

Ru-B/γ-Al2O3 catalyst was prepared by reductant impregnation method,which was applied in the selective hydrogenation of ethyl 1H-indole-2-carboxylate for producing ethyl 2,3,3a,7a-tetrahydro-1H-indole-2-carboxylate with hydrogen as reductant.Furthermore,we discussed the influences of substrate concentration,reaction solvent,hydrogenation temperature,initial hydrogen pressure and reaction time on the catalytic performance of the as-prepared catalyst.The obtained Ru-B/γ-Al2O3 catalyst showed a high-efficiency for the selective hydrogenation of ethyl 1H-indole-2-carboxylate（＞99％ conversion and selectivity） in i-propanol used as solvent at a concentration of 10％（mass fraction） of ethyl 1H-indole-2-carboxylate,a pressure of hydrogen of 6 MPa and a reaction temperature of 373 K.     

Lewis-acid promoted aromatic cyclization of α-chlorosulfides: Synthesis of ethyl isothiochroman-1-carboxylate and related compounds

A variety of ethyl isothiochroman-1-carboxylates and related compounds were synthesized by treatment of 2-chloro-2-[(2-arenyl)ethylthio]acetates with stannic chloride in methylene chloride. The same procedure was applied to the synthesis of ethyl 4-chloro-4-methyltetrahydrothiopyran-2-carboxylate. Some isothiochroman-1-carboxylic acids were prepared and evaluated for antiinflammatory activity. Among the compounds tested, 7-phenoxyisothiochroman-1-carboxylic acid showed weak activity.     

Stereospecific microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate

Microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate by the majority of evaluated microorganisms gave the ethyl cis-(3R,4R)-1-benzyl-3R-hydroxy-piperidine-4R-carboxylate as the major product in high diastereo- and enantioselectivities. The 3R,4R-hydroxy ester was produced in 97.4% diastereomeric excess (de) and 99.8% enantiomeric excess (ee) by Candida parapsilosis SC16347, while 99.5% de and 98.2% ee were obtained from reduction by Pichia methanolica SC16415. A few of the evaluated microorganisms gave 10–40% of the ethyl trans-(3R,4S)-1-benzyl-3R-hydroxy-piperidine-4S-carboxylate as the minor product.     

An efficient synthesis of 4H,5H-pyrano[3,4-c]pyran-4,5-diones from a suitably functionalized 2H-pyran-2-one

An efficient synthesis of ethyl 7-aryl-2-methyl-4H,5H-pyrano[3,4-c]pyran-4,5-dione-1-carboxylate 5, and ethyl 6-aryl-3-cyano-2H-pyran-2-one-4-acetate 6 has been delineated by reaction of suitably functionalized 2H-pyran-2-ones 1 with ethyl acetoacetate 2.     

Synthesis of 9-[(2-hydroxy-1-phosphonylethoxy)ethyl]guanine, 1-[(2-hydroxy-1-phosphonylethoxy)ethyl]cytosine and 9-[(2-hydroxy-1-phosphonylethoxy)ethyl] adenine

The acyclic nucleoside phosphonate analogues, 9-[(2-hydroxy-1-phosphonylethoxy)ethyl]guanine 6 , 1-[(2-hydroxy-1-phosphonylethoxy)ethyl]cytosine 7 and 9-[(2-hydroxy-1-phosphonylethoxy)ethyl]adenine 8 , have been prepared by the coupling of a tosylate of the phosphonate side chain 12 with a purine or pyrimidine base followed by deprotection of the blocking groups.     

Reaction of ethyl 3-ethoxymethylene-2,4-dioxovalerate and ethyl ethoxymethyleneoxaloacetate with 3-aminopyrazole analogs. Synthesis and chemistry of 3,6,7-trisubstituted pyrazolo[1,5-a]pyrimidine derivatives

The chemical reactivity of a series of 3-substituted-6-acetyl-7-carbethoxypyrazolo[l,5-a]pyrimidines ( 6a,b,c ) and 3-substituted-6,7-dicarbethoxypyrazolo[1,5-a]pyrimidines ( 7a,b,c ), prepared by the condensations of the 3-aminopyrazole analogs ( 3a,b,c ) with ethyl 3-ethoxymethylene-2,4-dioxovalerate ( 1 ) or ethyl 3-ethoxymethyleneoxaloacetate ( 2 ), was investigated. Catalytic hydrogenation of 6 or 7 afforded 4,7-dihydro derivatives ( 8 or 9 ). Treatment of 6a,b with acetic acid and water underwent ring transformation into 6H-pyrazolo[1,5-a][1,3]diazepin-6-ones ( 17a,b ). By treatment with phenylhydrazine compounds of type 6 underwent cyclization to yield 2H-dipyrazolo[1,5-a:4′,3′-e]pyrimidines ( 18a,b,c ). Compounds 6 or 7 were treated with an excess of diazomethane at room temperature to give 5-methyl-6H-cyclopropa[5a,6a]pyrazolo-[1,5-a]pyrimidines ( 24 and 25 ) in excellent yields. However, when this reaction was carried out under ice cooling, only compounds of type 23 were isolated. Reaction of 6a with ethyl diazoacetate is also described.     

Features of reactions of polyfluorinated ethyl 4-oxo-2-pnenyl-4H-chromene-3-carboxylates with N-nucleophiles

Ethyl 5,6,7,8-tetrafluoro-4-oxo-2-phenyl-4H-chromene-3-carboxylate in reactions with primary amines is characterized by a chromone-coumarin rearrangement affording 3-[amino(phenyl)methylene]-6,7,8-trifluoro-2H-chromene-2,4(3H)-diones, and ethyl 4-oxo-2-phenyl-5,6,7,8-tetrafluoro-4H-chromene-3-carboxylate characteristically adds the amine at the C² site of the flavone furnishing 3-amino-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)acrylates which depending on the substituent at the amino group are capable of intramolecular cyclization into 3-[(alkylamino)(phenyl)methylene]-5,6,7,8-tetrafluoro-2H-chromene-2,4(3H)-dione or in the case of benzylamine substituent, into ethyl 1-benzyl-5-hydroxy-4-oxo-2-phenyl-6,7,8-trifluoro-1,4-dihydroquinoline-3-carboxylate. The main process in the reaction of tri- and tetrafluoroflavones with secondary amine (1-methylpiperazine) is the nucleophilic substitution at the C⁷ of flavone. In the reaction with 1,2-phenylenediamine 3-[(2-aminophenyl)amino]-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)acrylate was obtained from tetrafluoroflavone and 1H-benzimidazol-2-yl(3,4,5-trifluoro-2-hydroxyphenyl)methanone, from trifluoroflavone.     

A practical synthesis of ethyl 1,2,4-triazole-3-carboxylate and its use in the formation of chiral 1′,2′-seco-nucleosides of ribavirin

A practical and efficient synthesis of ethyl 1,2,4-triazole-3-carboxylate ( 6a , R' = H) from ethyl carboethoxyformimidate hydrochloride ( 7 ) is described. Alkylation of this heterocycle with the chloromethyl ethers of 1,3-O-dibenzylbutane-1,2R,3S-triol ( 8a ) and 1,3,4-O-tribenzylbutane-1,2R,3S,4-tetrol ( 8b ), followed by conversion of the ester function to the amide and deprotection, furnished the chiral 1′,2′-seco-nucleosides of ribavirin, 11a and 11b , respectively.     

Condensation of ethyl 3-pyridylacetate with ethyl phenylpropiolate

Ethyl phenylpropiolate reacted with ethyl 3-pyridylacetate in the presence of sodium ethoxide to give ethyl 3,5-diphenyl-4-carbethoxy-6-(3-pyridyl)salicylate (III). Different derivatives for the product were prepared and their structures were elucidated on the basis of ir and nmr spectra.     

Unexpected reduction of ethyl 3-phenylquinoxaline-2- carboxylate 1,4-di-N-oxide derivatives by amines

The unexpected tendency of amines and functionalized hydrazines to reduce ethyl 3-phenylquinoxaline-2-carboxylate 1,4-di-N-oxide (1) to afford a quinoxaline 1c and mono-oxide quinoxalines 1a and 1b is described. The experimental conditions were standardized to the use of two equivalents of amine in ethanol under reflux for two hours,with the aim of studying the distinct reductive profiles of the amines and the chemoselectivity of the process. With the exception of hydrazine hydrate, which reduced compound 1 to a 3-phenyl-2-quinoxalinecarbohydrazide derivative, the amines only acted as reducing agents.     

Synthesis of certain exocyclic thiazole nucleosides related to tiazofurin. Formation of a unique acycloaminonucleoside

Several thiazole nucleosides structurally related to tiazofurin (1) and ARPP (2) were prepared, in order to determine whether these nucleosides had enhanced antitumor/antiviral activities. Ring closure of 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)thiourea (4) with ethyl bromopyruvate (5a) gave ethyl 2-(2,3,5-tri-O-benzoyl-β-D-ribofuranosylamino)thiazole-4-carboxylate (6a) . Treatment of 6a with sodium methoxide furnished methyl 2-(β-D-ribopyranosylamino)thiazole-4-carboxylate (9) . Ammonolysis of the corresponding methyl ester of 6a gave a unique acycloaminonucleoside 2-[(1R, 2R, 3R, 4R)(1-benzamido-2,3,4,5-tetrahydroxypentane)amino]-thiazole-4-carboxamide (7a) . Direct glycosylation of the sodium salt of ethyl 2-mercaptothiazole-4-carboxylate (12) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (11) gave the protected nucleoside 10 , which on ammonolysis provided 2-(β-D-ribofuranosylthio)thiazole-4-carboxamide (3b) . Similar glycosylation of 12 with 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride (13) , followed by ammonolysis gave 2-(2-deoxy-β-D-ribofuranosylthio)thiazole-4-carboxamide (3c) . The structural assignments of 3b, 7a , and 9 were made by single-crystal X-ray analysis and their hydrogen bonding characteristics have been studied. These compounds are devoid of any significant antiviral/antitumor activity in vitro.     

An unexpected synthesis and application of ethyl 2,4-bis(chloromethyl)-6-iodoquinoline-3-carboxylate

Research on Chemical Intermediates - An unexpected and direct synthesis of ethyl 2,4-bis(chloromethyl)-6-iodoquinoline-3-carboxylate (3) from the chlorotrimethylsilane (TMSCl)-promoted...     

6-氨基-2-取代吲哚-3-羧酸乙酯及其衍生物的合成与生物活性评价

以2,4-二硝基氯苯和乙酰乙酸乙酯为原料, 经过亲核置换、还原-环化协同反应, 合成了6-氨基-2-甲基吲哚-3-羧酸乙酯, 而后在催化剂作用下, 与乙酰乙酸乙酯反应生成烯胺, 环化合成9-羟基-2,7-二甲基吡咯(2,3-f)喹啉-3-羧酸乙酯; 类似地, 合成了6-氨基-2-苯基吲哚-3-羧酸乙酯和6-氨基-2-(呋喃-2'-基)吲哚-3-羧酸乙酯. 其结构均由¹H NMR, IR以及MS波谱数据表征. 所得化合物具有抑制肺癌A549细胞生长的活性, 其抑制效果具有浓度依赖性.