Search

Herein, we report a highly regioselective one-pot synthesis of pyrazolo[3,4-b]pyridines via the reaction of 3-arylidene-1-pyrrolines with aminopyrazoles. The reaction proceeds through the sequential nucleophilic addition/electrophilic substitution/C–N bond cleavage and provides easy access to pyrazolo[3,4-b]pyridine derivatives featuring a primary amino group. Moreover, the reaction can be terminated at the electrophilic substitution stage, thus providing convenient entry to the hardly accessible pyrazolopyrrolopyridine scaffold.

Self-organization of hydroxyethylated gemini surfactants with different spacer fragments 16-s-16(OH) (s = 4, 6, 10, and 12) was studied in single solutions and in binary surfactant-oligonucleotide systems. Despite the fact that aggregation activity and solubilization capacity of aggregates decrease with an increase in spacer length, gemini with the longer spacer demonstrate superior binding capacity toward oligonucleotide as compared to single head surfactant and gemini analogs with shorter spacers. The detailed study testified that gemini with longer spacers are characterized by a looser packing mode, a moist and more polar interior, and tend to show polymorphism. These features in combination with favorable geometry factor providing suitable orientation of components are probably responsible for the beneficial lipoplex formation in the case of longer spacers. The effectiveness of oligonucleotide-surfactant complexation changes in the same order as transfection efficacy mediated by these gemini reported earlier [Zakharova, L. et al. Colloids Surf. B, 2016, 140, 269–277], which indicates that physicochemical aspects probably play a key role upon the design of nonviral vectors and may be used for prediction of transfection efficacy mediated by amphiphilic agents.

Presented herein is a novel synthesis of new 2-(quinolin-4-yl)-1,4-dihydroquinazoline systems 8, in which the acid-catalyzed rearrangement of spiro[benzo[e][1,4]diazepine-3,4′-quinolin]-2(1H)-ones generated in situfrom 3-(2-aminophenyl)-5H-benzo[e][1,4]diazepin-2(1H)-ones 6with acetone and alkylmethyl ketones has been realized as an important step. An attempt to synthesize isomeric 2-(2-aminophenyl)-5H-benzo[e][1,4]diazepin-3(4H)-one 6′aby hydrolysis of the corresponding N-{2-[5H-benzo[e][1,4]diazepin-3(4H)-on-2-yl]phenyl}acetamide 5′aled to a new heterocyclic system, 6-methyl-8,13-dihydro-13aH-quinazolino[4,3-b]quinazolin-5-ium 13a-carboxylate 14, as a result of an unexpected rearrangement. In addition, it is noteworthy that during the hydrolysis of N-{2-[5H-benzo[e][1,4]diazepin-2(1H)-on-3-yl]phenyl}acetamides 5, the not previously described 14-dihydro-5H-14,5a-(epimino[1,2]benzo)benzo[5,6][1,4]diazepin[2,1-b]quinazolin-6(7H)-ones 7were unexpectedly obtained.

A novel and efficient protocol for the synthesis of diversely substituted 2,2′-bibenzimidazoles from the reaction of 3-cyanoquinoxalin-2(1H)-ones with 1,2-diaminobenzenes has been developed, which proceeds through sequential nucleophilic addition and electrophilic substitution followed by a Mamedov rearrangement. The synthetic utility of this strategy was illustrated by the concise, one-pot synthesis of 5,5′-bi(2,2′-bibenzimidazoles) and aza-analogues of 2,2′-bibenzimidazole.

A facile approach to a range of substituted 7-(benzimidazol-2-yl)thioxolumazines [7-(benzimidazol-2-yl)-2-thioxo-2,3-dihydropteridin-4(1H)-ones] and 7-(benzimidazol-2-yl)lumazines [7-(benzimidazol-2-yl)pteridine-2,4(1H,3H)-diones] is described. These new biheterocyclic systems are obtained via H2SO4-catalyzed rearrangement of quinoxalin-2-ones in the presence of 5,6-diamino-2-mercapto- and 2,5,6-triaminopyrimidin-4-ols. Thus, benzimidazole and pteridine rings are constructed in one synthetic step. A plausible ANRORC (addition of nucleophile, ring opening and ring closure)-type reaction mechanism is proposed. Applying the rearrangement to the aza-analogue of 3-benzoylquinoxalin-2(1H)-one—i.e., 3-benzoylpyrido[2,3-b]pyrazin-2(1H)-one—with 5,6-diamino-2-mercaptopyrimidin-4-ol makes it possible to synthesize inaccessible 7-(1H-imidazo[4,5-b]pyridin-2-yl)-6-phenyl-2-thioxo-2,3-dihydropteridin-4(1H)-one. 7-(Benzimidazol-2-yl)-6-(2-fluorophenyl)-2-thioxo-2,3-dihydropteridin-4(1H)-ones undergoes intramolecular nucleophilic substitution of fluorine by a nitrogen of the benzimidazole fragment with the formation of benzo[4′,5′]imidazo[1′,2′:1,2]quinolino[4,3-g]pteridine-2,4(1H,3H)-diones as new heterocyclic systems.

A facile and direct intramolecular indolinone-quinolone rearrangement was developed for the synthesis of quinolino[3,4-b]quinoxalin-6-ones from spiro[indoline-3,2′-quinoxaline]-2,3′-diones, which are readily available with use of isatines, malononitrile, and 1,2-phenylenediamines under quite mild conditions. This efficient approach provides excellent yields and could potentially be used for the construction of a diverse library of quinolino[3,4-b]quinoxalin-6-ones for high-throughput screening in medicinal chemistry. The reaction mechanism is explored by extensive DFT calculations.

Herein, we report a polyphosphoric acid (PPA)-mediated divergent metal-free operation to access a diverse collection of 3-(indol-2-yl)quinoxalin-2-ones and 4-(benzimidazol-2-yl)-3-methylcinnolines in moderate to excellent overall yields. The described process involves two distinct, and competing rearrangements of 3-(methyl(2-phenylhydrazono)methyl)quinoxalin-2-ones, namely [3,3]-sigmatropic Fischer rearrangement with the formation of an indole ring to produce 3-(indol-2-yl)-quinoxalin-2-ones, and Mamedov rearrangement with simultaneous construction of benzimidazole and cinnoline rings to form the new biheterocyclic system─4-(benzimidazol-2-yl)-3-methylcinnolines. The reaction mechanism of both rearrangement channels is explored by extensive dispersion-corrected DFT calculations. It is partcularly remarkable that when 3-(aryl(2-phenylhydrazono)methyl)quinoxalin-2-ones is used, instead of 3-(methyl(2-phenylhydrazono)methyl)quinoxalin-2-ones, reactions proceed regioselectively with the formation of only rearrangement products─4-(benzimidazol-2-yl)-3-arylcinnolines with high yields. This operationally simple protocol enables a rapid access to these scaffolds and is compatible with a wide scope of starting materials. In addition, the new rearrangement found features a promising approach for the design of unique compound libraries for drug design and discovery programs.

The aggregation behavior and catalytic activity of the polyethyleneimine (PEI) and sulfonatomethylated calix[4]resorcinarene (SCA) based systems are studied by methods of the NMR and UV−vis spectroscopy. The investigation of the kinetics of hydrolysis of the p-nitrophenyl dimethyl phosphate revealed two reaction routes in both the single PEI solution and the binary PEI-SCA system. Although SCA alone shows no catalytic activity, a 10-fold synergetic catalytic effect is achieved in the binary PEI-SCA system as compared to the single PEI systems at the SCA concentrations below the critical micelle concentration (cmc) of 0.011 M originating from the tensiometry data. The inclusive type of interactions involving the calixarene cavity is shown to contribute to the PEI-SCA self-assembly in the concentration range below this cmc value, which is probably responsible for the above rate acceleration. The different modes of self-organization assuming the PEI inclusion into the calixarene cavity are discussed.

Novel cationic amphiphiles of the 3-alkyl-1-(4-methoxyphenyl)-1H-imidazol-3-ium bromide series bearing methoxyphenyl fragments (MPI-n) have been synthesized. Their aggregation properties in aqueous solutions, solubilization capacity, and hemolytic and antimicrobial activities have been investigated by a number of physicochemical methods. Using tensiometry, conductometry, and fluorescence spectroscopy, it was shown that the MPI-nhave lower CMCs than their nonfunctionalized counterparts. The unusual alkyl-chain-length-dependent morphology of aggregates is testified for this homological series. Amphiphiles with 12, 14, and 16 alkyl tails are characterized by the formation of micellar aggregates, while a surfactant with a decyl tail is characterized by the formation of larger aggregates with lower surface curvature. The MPI-10 aggregate morphology was rationalized in terms of the packing parameter consideration and was supported by size measurements and the fluorescence probe techniques, which showed that vesicle-like aggregates in close-packing mode probably occur. MPI-naggregates have exhibited a high solubilization capacity toward hydrophobic azo dye Orange OT. Importantly, amphiphiles studied showed (i) high bacteriostatic activity at the level of ciprofloxacin; (ii) high bactericidal action against all Gram-positive bacteria, including methicillin-resistant strains; (iii) bactericidal properties against Gram-negative bacteria; and (iv) low hemolytic activity.

A new process has been developed for the bromine-promoted sequential (sp2)C = (sp2)C bond functionalization of (E)-3-styrylquinoxalin-2(1H)-ones and furo[b]annulation via the 5-exo-cyclization in dimethyl sulfoxide (DMSO). The reaction represents a novel strategy for the synthesis of 2-aryl-3-(methylthio)furo[2,3-b]quinoxalines and involves 3-(1,2-dibromo-2-arylethyl)quinoxalin-2(1H)-ones and 2-arylfuro[2,3-b]quinoxalines as key intermediates. Furthermore, DMSO was converted to dimethyl sulfide in situ, which served as the methylthiolation reagent in the reaction. This protocol constitutes an efficient and convenient method for the annulation and methylthiolation of (E)-3-styrylquinoxalin-2(1H)-ones bearing a wide range of functional groups in high yields at room temperature.

The catalytic system can be reused with only a small loss of activity.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.