Synthesis and properties of 2,7-phenylethenyl- and benzoxazol-2-ylethenyl <Emphasis Type="Italic">N</Emphasis>-ethylcarbazole derivatives

A number of new symmetrically and unsymmetrically substituted 2,7-phenylethenyl and benzoxazol-2-ylethenyl N-ethylcarbazole derivatives were synthesized by successive Wittig and Knoevenagel olefinations of 9-ethylcarbazole-2,7-dicarbaldehyde. The resulting compounds showed strong photoluminescence in the blue region. The spectral parameters of unsymmetrically substituted 9-ethylcarbazoles with a donor-donor-acceptor conjugation type are determined by intramolecular interaction in the donor-acceptor fragment.     

Reduction of 4-arylazoindoles

It was established that 4-acetamido-5-hydroxyindole derivatives are formed in the reduction of 4-phenylazo-5-hydroxyindole derivatives with zinc dust in acetic acid in the presence of acetic anhydride and sodium acetate. However, p-semidine rearrangement of the intermediate hydrazo derivatives is observed in the analogous reduction of 4-arylazo-5-methoxyindoles, and 4-acetamido-5-methoxy-7-arylaminoindoles are formed. The latter are oxidized by oxygen and nitric acid to 4-oxo-7-arylimino-4,7-dihydroindoles; nitration of the arylimino ring occurs in some cases under the influence of nitric acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1374–1379, October, 1980.     

Functional derivatives of thiophene. I. Synthesis and 1H-NMR spectra in the 2-aminothiophene series

The preparation of 2-amino-5-nitrothiophene, 2-formamido-5-nitrothiophene, 2-acetamido-5-nitrothiophene and 2-t-butyloxycarbonylamino-5-nitrothiophene are described. Abnormal values of the coupling constants J_3.4 had been observed in the ¹H-nmr spectra of compounds obtained.     

Synthesis and reactions of pyrido[3,2,1‐jk]carbazole‐4,6‐diones

Pyrido[3,2,1‐jk]carbazoles 1 , synthesized from carbazoles and alkyl‐ or arylmalonates, gave regioselective electrophilic substitution reactions at position 5 such as chlorination to 5‐chloro derivatives 2 , nitration to 5‐nitro compounds 3 , or hydroxylation to 5‐hydroxy derivatives 4 . 5‐Hydroxy compounds 4 gave on treatment with strong bases ring contraction to 5 , 6 or the ring opening product 7 . Exchange of the chloro group in 2 with azide or amines gave the corresponding azides 8 and the 5‐amino derivatives 9 and 10 . Alkylation of 1 with benzyl chloride or allyl bromide resulted in the formation of 5‐C‐alkylated products 11 together with 4‐alkyloxy derivatives 12 . J. Heterocyclic Chem., 48, 1039 (2011).     

Synthetic Studies on Sialoglycoconjugates 14: Synthesis of Ganglioside GM3 Analogs Containing The Carbon 7 And 8 Sialic Acids

ABSTRACT

Ganglioside GM₃ analogs, containing 5-acetamido-3, 5-dideoxy-L-arabino-heptulosonic acid and 5-acetamido-3, 5-dideoxy-D-galacto-octulosonic acid have been synthesiyed. Glycosylation of 2-(trimethylsilyl)ethyl 0-(6-0-benzoyl-ß-D-galactopyranosyl)-(l→4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (5), with methyl (methyl 5-acetamido-4, 7-di-0-acetyl-3, 5-dideoxy-2-thio-ß-L-arabino-2-heptulo-pyranosid)onate (2) or with methyl (methyl 5-acetamido-4, 7, 8-tri-0-acetyl-3, 5-dideoxy-2-thio-α-D-galacto-2-octulopyranosid)onate (4), which were respectively prepared from the corresponding 2-S-acetyl derivatives (1 and 3) by selective 2-S-deacetylation and subsequent S-methylation, using dimethyl(methylthio)sulfonium triflate as a glycosyl promoter, gave 2-(trimethylsilyl)ethyl 0-(methyl 5-acet-amido-4, 7-di-0-acetyl-3, 5-dideoxy-ß-L-arabino-2-heptulopyranosyl-onate)-(2→3)-0-(6-0-benzoyl-ß-D-galactopyranosyl)-(1→4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (6) and 2-(trimethylsilyl)ethyl (0)-(methyl 5-acetamido-4, 7, 8-tri-0-acetyl-3, 5-dideoxy-α-D-galacto-2-octulopyranosylonate)-(2→3)-0-(6-0-benzoyl-ß-D-galactopyranosyl)-(l-4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (10), respectively. Compounds 6 and 10 were converted, via 0-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the corresponding trichloroacetimidates 9 and 13, respectively.

Glycosylation of (2S, 3R, 4E)-2-azido-3-0-benzoyl-4-octadecen1, 3-duik (14) with 9 or 13 affored the ß-glcosides (15 and 18), which were converted, via selective reduction of the azide group, coupling with octadecanoic acid, 0-deacylation, and deesterification, into the title compounds, respectively.     

β-Carbolines as agonistic or antagonistic benzodiazepine receptor ligands. 1. Synthesis of some 5-, 6- and 7-amino derivatives of 3-methoxycarbonyl-β-carboline (β-CCM) and of 3-ethoxycarbonyl-β-carboline (β-CCE)

Condensation of diethyl formylamino- or diethyl acetylaminomalonate with 4-, 5- or 6-nitrogramine 1 afforded the diethyl formylamino- or the diethyl acetylamino[(nitroindol)-3-ylmethyl]malonates 2 ; reduction of the nitro group followed by N-formylation or acetylation of the resulting amino compounds 3 , led to the 4-, 5-and 6-acylamino derivatives 4 . Cyclization of 4 in the presence of polyphosphoric esters gave the 3,3-bis(ethoxycarbonyl)-3,4-dihydro-β-carbolines 5 , which underwent lithium chloride/water catalyzed monodeethoxycarbonylation to the corresponding 5-, 6- and 7-acylamino-3-ethoxycarbonyl-β-carbolines 6 , whose acidic hydrolysis led finally to the 5-, 6- and 7-amino-3-ethoxycarbonyl-β-carbolines 9 . The 6-amino compounds 9b-e were obtained also by direct nitration of 3-methoxycarbonyl-β-carboline 7a and of 3-ethoxycarbonyl-β-carboline 7c , followed by the nitro group reduction of the resulting nitro carbolines 8 . Preliminary studies of the binding to rabbit brain benzodiazepine receptor sites indicate compounds 9b and 9c to inhibit the ³H-diazepam binding at 10^?8 M concentrations.     

Polycondensed nitrogen heterocycles. Part 17. Isoxazolo[4,3-d]pyrazolo[3,4-f][1,2,3]triazepine. A new ring system

The title compounds were prepared by nitration of compounds 2 , reduction of the dinitro derivatives 4 and diazotization of the diamino derivatives 6 followed by an intramolecular coupling reaction. Compound 4a showed good activity against Salmonella cholerasuis and Clostridium perfringens bacteria.     

Synthesis and electrophilic substitutions of novel pyrazolo[1,5-c]-1,2,4-triazolo[4,3-a]pyrimidines

5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines 1 were used as precursors for the preparation of a new series of 5-aryl-8-phenylpyrazolo[1,5-c]-1,2,4- triazolo[4,3-a]pyrimidines 2. The reactions of 2 with certain electrophilic reagents gave the respective 6-substituted derivatives 3-5 rather than the 7-isomeric products. Formylation of the key compounds 1 with ethyl formate yielded the formyl derivatives 6. Furthermore, boiling of compounds 1 with acetic acid afforded 7-acetylhydrazino-5-aryl-2-phenylpyrazolo[1,5-c]pyrimidines 7. Bromination of 7 yielded the dibromo- derivatives 8, while their iodination and nitration gave the monosubstituted derivatives 9 and 10, respectively. Also, treatment of 1 with boiling acetic anhydride yielded the triacetyl derivatives 11. The structure of synthesized products was confirmed by elemental analyses, IR, 1H NMR and MS spectra.     

Selective scavenging property of the indole moiety for the nitrating species of peroxynitrite

The inhibitory effect on tyrosine nitration and oxidation of peroxynitrite was evaluated for more than 40 reagents including natural and synthetic compounds, and the inhibiting efficiency of each compound for nitration was compared with that for oxidation, to characterize its property as a peroxynitrite scavenger. In the presence of various concentrations of testing compounds, the nitrating and oxidizing activities were measured by monitoring the formation of 3-nitrotyrosine and dityrosine with an HPLC-UV-fluorescence detector. The IC(50) values for nitration and oxidation were determined, and the ratio of these two IC(50) values was calculated for each compound. Although the IC(50) values varied from compound to compound, it was revealed that the ratio of two IC(50) values (IC(50) for oxidation/IC(50) for nitration) was 1 in almost all the compounds tested, except five indole derivatives (L-tryptophan, melatonin, 5-methoxytryptamine, tryptamine, and tetrahydro-beta-carboline) and one synthetic selenium-containing compound ((2R,3R,4S)-2-amino-3,4-dihydroxy-5-phenylselenopentan-1-ol, ADPP). The indole derivatives showed a specific inhibitory effect on tyrosine nitration without affecting the oxidation. ADPP was confirmed to have a preferable inhibitory activity for tyrosine oxidation. It was suggested that compounds showing an IC(50) value ratio of 1 scavenged the common species for nitration and oxidation, while the indole derivatives and ADPP preferably scavenged the nitrating and oxidizing species, respectively. From a stopped flow study, it was also revealed that the nitrotyrosine formation was relatively slow, unlike an OH radical reaction. These results imply that the peroxynirite reaction at least partly proceeds through specific species for nitration.     

Synthesis of Some Halogen- and Nitro-substituted Nicotinic Acids and Their Fragmentation Under Electron Impact

Features of electrophilic and nucleophilic substitution under chlorination and nitration reactions conditions have been investigated for 6-hydroxy- and 6-methyl-substituted derivatives of 3-cyano-4-methyl-2(1H)-pyridones. The polychloro- and nitro-substituted 3-cyano-4-methylpyridines obtained were used as synthons in the synthesis of some polyhalo- and nitro-substituted nicotinic acids and their amides. The fragmentation pathways of the synthesized compounds under electron impact have been studied.     

Stereospecific synthesis of cis- and trans-4-amino-3-hydroxythiophanes

The reduction of 4-benzoylamino- and 4-carbethoxyamino-3-ketothiophanes proceeds stereospecifically to form only trans-4-benzoylamino- and trans-4-carbethoxyamino-3-hydroxythiophanes, respectively, from which trans-4-amino-3-hydroxythiophane is obtained by alkaline hydrolysis. It was established that acid hydrolysis of trans-4-carbethoxyamino-3-hydroxythiophane leads only to trans-4-amino-3-hydroxythiophane, while acid hydrolysis of trans-4-benzoylamino-3-hydroxythiophane is accompanied by inversion to form cis-4-amino-3-hydroxythiophane. Derivatives of the cis- and trans-isomeric pairs of 4-amino-3-hydroxythiophanes were synthesized.Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 12, pp. 1609–1613, December, 1970.     

Nitration in the carbazole series

Nitration of9-tosylcarbazole in acetic anhydride solution gives l-nitro (28%), 2-nitro (19%) and 3-nitro (53%) derivatives. The mixture of the nitro compounds obtained from 9-acetylcarbazole contains 10%, 48% and 42% of the isomers, respectively. Under similar conditions 9-nitrosocarbazole shows a different isomer distribution: 34% of 1-nitro and 66% of 3-nitrocarbazole. Nitration of carbazole is a two step process involving formation and rearrangement of 9-nitrocarbazole. The hypothesis was supported by the results of 1,3,6,8-tetrachlorocarbazole nitration and oxidation of 9-nitrosocarbazole and rearrangement of 9-nitrocarbazole in the nitration conditions.     

吡啶硝化衍生物的合成及应用

综合评述了吡啶类化合物的硝化合成方法及近年来的研究进展，对其中较重要的氮氧化－硝化法进行了讨论，并介绍了该类衍生物在农药、医药、有机合成等方面的应用情况。     

Synthesis and some transformations of new 9-furylnaphtho[2,3-b]furan derivatives

The synthesis of a number of naphtho[2,3-b]furan derivatives, containing a furyl substituent in position 9 by intramolecular cyclization of 2-carboxy and 2-formylbis(5-alkylfur-2-yl)methanes is described. The reactivity of the title compounds in formylation, acetylation, nitration, and oxidation reactions has been investigated. It was shown that nitration of 2-methyl-9-(5-methyl-2-furyl)naphtho[2,3-b]furan-4-yl acetate leads to oxidative furan ring opening rather than to electrophilic substitution.     

Electrophilic substitution of acetamido- and acetoxybenzo-1,4-dioxanes

The products of acylation, bromination, and nitration of 5- and 6-acetamido- and 5- and 6-acetoxybenzo-1, 4-dioxanes were established. It is shown on the basis of calculations by the self-consistent field (SCF) MO LCAO method that the directions of the electrophilic substitution reactions of these derivatives and of benzo-1,4-dioxane correspond to the -electron population of the AO of the carbon atoms of the aromatic ring stipulated by the boundary occupied MO.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 467–473, April, 1977.     

Synthesis of 4-deoxy-4-nitrosialic acid

The synthesis of 4-deoxy-4-nitrosialic acid (3,4,5-trideoxy-4-nitro-D-glycero-beta-D-galacto-non-2-ulopyranosonic acid, 5), was completed in seven steps starting from D-arabinose. Coupling of the 6-carbon fragment, 2-acetamido-1,2-dideoxy-1-nitro-D-mannitol (6) with ethyl alpha-(bromomethyl)acrylate afforded a 2 : 1 mixture of ethyl 5-acetamido-2,3,4,5-tetradeoxy-2-methylene-4-nitro-D-glycero-D-galacto-nononate (9a-S) and ethyl 5-acetamido-2,3,4,5-tetradeoxy-2-methylene-4-nitro-D-glycero-D-talo-nononate (9a-R). This mixture of enones was subjected to ozonolysis, and following reduction of the ozonide, the resultant products cyclised to the pyranosides. The target compound, ethyl 4-deoxy-4-nitrosialate (11a) was isolated by fractional crystallisation. Hydrolysis of the ethyl ester proved problematic; thus, the synthesis was modified by using tert-butyl alpha-(bromomethyl)acrylate. Following ozonolysis of the corresponding tert-butyl enoate esters and diastereomer separation, the tert-butyl ester of 4-nitrosialic acid (11b) could be deprotected under acidic conditions to afford . The target compound is a useful intermediate for synthesis of a variety of C-4 substituted sialic acid derivatives, and it is synthesised by a modular route.     

Synthetic Studies on Sialoglycoconjugates 7: Synthesis of N-Acetylneuraminic Acid Derivatives and Analogs

ABSTRACT

Various types of the O-protected derivatives and the 9-bromo analogs of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate were synthesized from methyl [2-(trimetnyl-silyl)ethyl 5-acetamido-4, 7-di-O-acetyl-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) or methyl [2-(trimethylsilyl)ethyl 5-acetamido-8, 9-di-O-isopropylidene-D-glycero-α-D-galacto-2-nonulopyranosidlonate (3).     

Bromination,nitration, and azo coupling of substituted 3-ethoxycarbonyl-5-hydroxybenzofurans

The bromination and nitration of 2-methyl-3-ethoxycarbonyl-5-hydroxybenzofuran (I) leads to 6-bromo and 6-nitro derivatives, while azo coupling results in substitution of the hydrogen in the 4 position. The structures of the compounds obtained were confirmed by IR and PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1443–1446, November, 1971     

Investigation of 2, 1, 3-thia- and 2, 1, 3 selenadiazoles

The nitration of naphtho[1,2-d][2,1,3]thiadiazole under the conditions that are normally used for aromatic compounds gives a mixture of 6- and 9-nitronaphthothiadiazoles, which can be reduced to 6- and 9-amino derivatives, respectively. 6-Hydroxynaphthothiadiazole is obtained from 6-aminonaphthothiadiazole by the Sandmeyer reaction, while 8-hydroxynaphthothiadiazole is converted to the 8-amino derivative under the conditions of the Bucherer reaction. 4-Carboxy-5-(o-carboxyphenyl)-2,1,3-thiadiazole was obtained by the oxidation of naphtho[1,2-d][2,1,3]-thiadiazole with a potassium dichromate-dilute sulfuric acid mixture.See [1] for communication LXVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1496–1502, November, 1972.     

as-Triazino[4,5-α] indoles. III. Etude des substitutions électrophiles des triazinoindolones

Electrophilic substitution reactions of the 1- and 4-triazino-indolones were made on lactamic nitrogen with methyl sulphate or benzyl chloride and on the homocycle with bromine or nitric acid. BrominatJon and nitration reactions gave either mono-substitutions on position 10 or disubstitutions on position 7 and 10 or 9 and 10 or polysubstitutions leading to mixtures of tri-and tetrasubstituted compounds. The structure of the derivatives was determined by nmr, study of the NOE effect and unequivocal synthesis.