[Show abstract][Hide abstract] ABSTRACT: The tuning of selective ring closure is a nontrivial challenge in synthetic organic chemistry. Herein we report a solvent switchable metal-free [4 + 2] cycloaddition approach via Csp2–H functionalization. The protocol is highly atom economical with water being the only by-product, delivering N-subsituted benzo[e]- or [f]isoindolones in high yields.
[Show abstract][Hide abstract] ABSTRACT: A cascade transformation involving the Ugi reaction followed by 5-endo-dig carbocyclization and retro-Claisen fragmentation providing access to a 1H-pyrrol-2(5H)-one core is described. The operating protocol is very similar to the typical Ugi reaction settings, while the overall outcome results from the application of a 3-substituted propiolic acid and a phenylglyoxal as acid and aldehyde components, respectively. The utility of process is demonstrated through the synthesis of a small library of 5-oxo-2,5-dihydro-1H-pyrrole-2-carboxamides.
Annalen der Chemie und Pharmacie 09/2014; · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The usual way to synthesize spiroindolinones is the application of isatin derivatives. Here, we report the first Pd-catalyzed Buchwald–Hartwig addition–elimination strategy for the formation of the spiroindolinone–isoindolinone architecture. The application of the Ugi-4-component reaction (Ugi-4CR) allows the facile introduction of diversity and increases the practicality of this protocol.
Annalen der Chemie und Pharmacie 09/2014; · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A three-component reaction of a 2-aminoazine, a 2-oxoaldehyde, and a cyclic 1,3-dicarbonyl compound providing access toward a novel class of imidazo[1,2-a]azine derivatives was developed and studied. The scope of the process was thoroughly explored under three different reaction conditions resulting in the generation of a small library of title compounds and highlighting the possibility of case-specific approach.
[Show abstract][Hide abstract] ABSTRACT: An efficient microwave-assisted synthesis of tertiary propargylamines has been developed by copper(I)-catalyzed decarboxylative A3-coupling reaction of an alkynylcarboxylic acid with a secondary amine and an aldehyde. A wide range of diversely substituted propargylamines could be synthesized in high yields. The optimal reaction conditions are also effective for 3-alkylpropiolic acids and for terminal propiolic acid.
Annalen der Chemie und Pharmacie 07/2014; · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A novel access to spiro[indoline-3,2'-pyrrole]-2,5'-diones is presented via a palladium-catalyzed post-Ugi cascade cyclization approach involving a Buchwald-Hartwig/Michael reaction sequence. The method allows the easy construction of a library of spirooxindoles in moderate to good yields starting from readily available precursors. In addition, alkynoic acids are replaced with α,β-unsaturated acids leading to variably substituted spirooxindoles.
[Show abstract][Hide abstract] ABSTRACT: A microwave-assisted protocol was developed for the construction of 2-amino-1H-imidazole/triazole conjugates starting from the previously described 2-hydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-4-ium salts. The process involves a one-pot hydrazinolysis/Dimroth-rearrangement of these salts followed by a ligand-free copper nanoparticle-catalyzed azide-alkyne Huisgen cycloaddition. The 2-amino-1H-imidazole/triazole conjugates showed moderate to high preventive activity against biofilms of S. Typhimurium, E. coli, P. aeruginosa and S. aureus. The most active compounds had BIC50 values between 1.3 and 8 μM. A remarkable finding was that introduction of the triazole moiety into the side chain of 2-aminoimidazoles with a long (C8-C13) 2N-alkyl chain did drastically improve their activity. Conclusively, the 2-amino-1H-imidazole/triazole scaffold provides a lead structure for further design and development of novel biofilm inhibitors.
[Show abstract][Hide abstract] ABSTRACT: A simple protocol for the synthesis of mono-propargylic amines (IV), (VI), (VIII), (XI), and (XIV) as well as symmetrical dipropargylic amines (XV) from α-amino esters, aldehydes or ketones, and alkynes.
[Show abstract][Hide abstract] ABSTRACT: The Ugi four-component reaction of 2-pyrrole aldehydes and analogous indole and benzothiophene aldehydes with primary amines, isonitriles, and alkynoic acids offers the expected adducts (V), (XI), and (XIV) which can be readily used for the synthesis of various fused pyridones and azepinones.
[Show abstract][Hide abstract] ABSTRACT: Cationic gold-catalyzed cycloisomerizations of propargylureas, derived in situ from secondary propargylamines and aryl or alkyl isocyanates, have been studied. The reaction outcome was found to be different from what was previously observed for the tosyl isocyanate-derived ureas in terms of both regio- and chemoselectivity. As a result, the current protocol offers efficient access to the 3,4-dihydropyrimidin-2(1H)-one core through the 6-endo-dig N-cyclization.
[Show abstract][Hide abstract] ABSTRACT: A highly efficient approach for the regioselective construction of fused nine-membered rings (diazoninone framework) was developed by employing sequential Ugi and gold-catalyzed intramolecular hydroarylation reactions. The scope of this intramolecular cyclization has been demonstrated.
European Journal of Organic Chemistry 01/2014; · 3.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and HeLa). A subset of monosubstituted 5-aryl-2-aminoimidazoles showed a moderate safety window, with therapeutic indices (TIs) ranging between 3 and 20. Whereas introduction of a (cyclo-)alkyl chain at the N1-position strongly reduced the TI, introduction of a (cyclo-)alkyl chain or a triazole moiety at the 2N-position increased the TI up to 370. Since a promising application of preventive anti-biofilm agents is their use in anti-biofilm coatings for orthopedic implants, their effects on cell viability and functional behavior of human osteoblasts and bone marrow derived mesenchymal stem cells were tested. The 2N-substituted 5-aryl-2-aminoimidazoles consistently showed the lowest toxicity and allowed survival of the bone cells for up to 4 weeks. Moreover they did not negatively affect the osteogenic differentiation potential of the bone cells. Finally, we examined the effect of the compounds on the survival of Caenorhabditis elegans, which confirmed the higher safety window of 2N-substituted 5-aryl-2-aminoimidazoles.
[Show abstract][Hide abstract] ABSTRACT: A microwave-assisted synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles from a phenylazide, propargyloxybenzaldehyde and a 1,2-diaminobenzene is proposed.
[Show abstract][Hide abstract] ABSTRACT: The intramolecular hydroarylation of Ugi adducts (V) in the presence of an indium catalyst leads to azepinoindolones (VI), whilst azocineindolones (VII) are obtained using a gold catalyst.
[Show abstract][Hide abstract] ABSTRACT: Nitrogen containing compounds are of great importance because of their interesting and diverse biological activities. The construction of the C-N bond is of significant importance as it opens avenues for the introduction of nitrogen in organic molecules. Despite significant advancements in this field, the construction of the C-N bond is still a major challenge for organic chemists, due to the involvement of harsh reaction conditions or the use of expensive catalysts in many cases. Thus, it is a challenge to develop alternative, milder and cheaper methodologies for the construction of C-N bonds. Herein, we have selected some prime literature reports that may serve this purpose.
Chemical Society Reviews 09/2013; · 24.89 Impact Factor