ABSTRACT
A new method for the direct synthesis of primary and secondary amides from carboxylic acids is described using Mg(NO3)2·6H2O or imidazole as a low-cost and readily available catalyst, and urea as a stable, and easy to manipulate nitrogen source. This methodology is particularly useful for the direct synthesis of primary and methyl amides avoiding the use of ammonia and methylamine gas which can be tedious to manipulate. Furthermore, the transformation does not require the employment of coupling or activating agents which are commonly required.
ABSTRACT
The trans-sialidase protein expressed by Trypanosoma cruzi is an important enzyme in the life cycle of this human pathogenic parasite and is considered a promising target for the development of new drug treatments against Chagas' disease. Here we describe α-amino phosphonates as a novel class of inhibitor of T. cruzi trans-sialidase. Molecular modelling studies were initially used to predict the active-site binding affinities for a series of amino phosphonates, which were subsequently synthesised and their IC50s determined in vitro. The measured inhibitory activities show some correlation with the predictions from molecular modelling, with 1-napthyl derivatives found to be the most potent inhibitors having IC50s in the low micromolar range. Interestingly, kinetic analysis of the mode of inhibition demonstrated that the α-aminophosphonates tested here operate in a non-competitive manner.
Subject(s)
Chagas Disease/drug therapy , Glycoproteins/antagonists & inhibitors , Neuraminidase/antagonists & inhibitors , Organophosphonates/chemistry , Organophosphonates/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/enzymology , Amination , Chagas Disease/parasitology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glycoproteins/chemistry , Glycoproteins/metabolism , Humans , Molecular Docking Simulation , Neuraminidase/chemistry , Neuraminidase/metabolism , Trypanosoma cruzi/drug effectsABSTRACT
A formal enantioselective synthesis of nectrisine, a potent α-glucosidase inhibitor, was carried out starting from butadiene monoepoxide through a synthetic sequence involving enantioselective allylic substitution, cross-metathesis, dihydroxylation, and cyclization.
Subject(s)
Glycoside Hydrolase Inhibitors/chemical synthesis , Imino Furanoses/chemical synthesis , Palladium/chemistry , Amination , Amines/chemical synthesis , Butadienes , Catalysis , Cyclization , Hydroxylation , Indicators and Reagents , Magnetic Resonance Spectroscopy , StereoisomerismABSTRACT
We report a new method for the conversion of nitroalkanes into carboxylic acids that achieves this transformation under very mild conditions. Catalytic amounts of iodide in combination with a simple zinc catalyst are needed to give good conversions into the corresponding carboxylic acids.
ABSTRACT
A simple, mild and general procedure for the hydration of nitriles to amides using copper as catalyst and promoted by N,N-diethylhydroxylamine is described. The reaction can be conducted in water at low temperature in short reaction times. This new procedure allows amides to be obtained from a wide range of substrates in excellent yields.
ABSTRACT
D- and L-carbocyclic nucleosides were obtained by a new procedure involving an enantioselective rhodium/duphos-catalyzed hydroacylation reaction as the key step. The 3-hydroxymethyl-cyclopentanol intermediate was obtained by stereoselective reduction of ketone and by dynamic kinetic resolution (DKR).