RESUMO
An enantioselective Brønsted acid-catalyzed N-acyliminium cyclization cascade of tryptamines with enol lactones to form architecturally complex heterocycles in high enantiomeric excess has been developed. The reaction is technically simple to perform as well as atom-efficient and may be coupled to a gold(I)-catalyzed cycloisomerization of alkynoic acids whereby the key enol lactone reaction partner is generated in situ. Employing up to 10 mol % bulky chiral phosphoric acid catalysts in boiling toluene allowed the product materials to be generated in good overall yields (63-99%) and high enantioselectivities (72-99% ee). With doubly substituted enol lactones, high diastereo- and enantioselectivities were obtained, thus providing a new example of a dynamic kinetic asymmetric cyclization reaction.
Assuntos
Ciclização , Compostos Heterocíclicos/síntese química , Catálise , Lactonas/química , Fenômenos de Química Orgânica , Estereoisomerismo , Triptaminas/químicaRESUMO
Modification of the ring nucleus of tetramic acids derived from serine gives chiral heterocyclic libraries that exhibit antibacterial activity, and correlation with various physicochemical parameters indicates that chiral tetramic acids may provide a potentially valuable non-aromatic skeleton for fragment-based drug discovery.
Assuntos
Antibacterianos/química , Descoberta de Drogas , Pirrolidinonas/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Estrutura Molecular , Pirrolidinonas/síntese química , Pirrolidinonas/farmacologia , Staphylococcaceae/efeitos dos fármacos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A direct enantio- and diastereoselective N-acyliminium cyclization cascade through chiral phosphoric acid catalyzed condensation of tryptamines with γ- and δ-ketoacid derivatives to provide architecturally complex heterocycles has been developed. The reaction is technically simple to perform, atom-efficient, and broad in scope. Employing 10 mol % of (R)-BINOL derived chiral phosphoric acids in refluxing toluene allowed the polycyclic product materials to be generated in good yields (53-99%) and moderate to high enantioselectivities (68-98% ee).