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Síntesis y actividad antifúngica in vitro frente a Fusarium oxysporum de amidas N-alquilsustituidas derivadas de 2-aminoácidos
Synthesis and in vitro antifungal activity against Fusarium oxysporum of N-alkyl-substituted amides derived from 2-amino acids
Síntese e atividade antifúngica in vitro contra Fusarium oxysporum de amidas N-alquil-substituídas derivadas de 2-aminoácidos
DOI:
https://doi.org/10.15446/rev.colomb.quim.v51n3.107148Palabras clave:
amidas N-alquilsustituidas, derivados de 2-aminoácidos, Fusarium oxysporum (es)N-alkyl-substituted amides, 2-amino acid derivatives, Fusarium oxysporum (en)
amidas N-alquilsubstituídas, Derivados de 2 aminoácidos, Fusarium oxysporum (pt)
Una serie de amidas N-alquilsustituidas 1-16 fueron sintetizadas a partir de malonato de dietilo y ésteres de alquilo derivados de los aminoácidos ʟ-triptófano, ʟ-alanina, ʟ-fenilalanina y ʟ-tirosina. Los métodos de síntesis empleados involucraron calentamiento por irradiación de microondas empleando tanto un ácido de Lewis (AlCl3) o 4-dimetilaminopiridina (DMAP) como catalizador y auxiliar nucleofílico, respectivamente. Los resultados sugieren que el uso de irradiación de microondas y de DMAP conlleva mejores rendimientos en un tiempo de reacción más corto. Para ilustrar las diferencias observadas, se presentan las propuestas mecanísticas de cada método de reacción para la formación de amidas N-alquilsustituidas. Finalmente, las amidas sintetizadas se evaluaron en condiciones in vitro frente a Fusarium oxysporum; mostraron actividad antifúngica a diferentes niveles (0,40 mM < IC50 < 29,1 mM), lo cual indicó que las variaciones de la actividad observada de este grupo de compuestos pueden deberse al efecto de la amida acíclica como bioisóstero no clásico de algunas fitoalexinas heterocíclicas.
N-alkyl substituted amides 1-16 were synthesized from diethyl malonate and alkyl esters derived from the amino acids ʟ-tryptophan, ʟ-alanine, ʟ-phenylalanine, and ʟ-tyrosine. In addition, a microwave-assisted protocol was employed using a Lewis acid (AlCl3) or dimethylaminopyridine (DMAP) as a catalyst and nucleophilic auxiliary, respectively, affording the desired compounds. The results suggest that DMAP-catalyzed reactions under microwave irradiation yield higher during short reaction times. Each reaction method's mechanistic proposals for forming N-alkyl-substituted amides are presented to illustrate the observed differences. The synthesized amides were evaluated under in vitro conditions against Fusarium oxysporum. The compounds exhibited antifungal activity at different levels (0.40 mM < IC50 < 29.1 mM). These results indicated that the observed activity variations of this compound group might be due to the effect of acyclic amide as a non-classical bioisostere of some heterocyclic phytoalexins.
Uma série de amidas N-alquil substituídas foram sintetizadas a partir de malonato de dietila e ésteres alquílicos derivados dos aminoácidos ʟ-triptofano, ʟ-alanina, ʟ-fenilalanina e ʟ-tirosina. Os métodos de síntese empregados foram realizados usando aquecimento por irradiação de micro-ondas empregando um ácido de Lewis (AlCl3) ou dimetilaminopiridina (DMAP) como catalisador. Os resultados sugerem que a irradiação de micro-ondas usando DMAP leva a melhores rendimentos em um tempo de reação mais curto. Para ilustrar as diferenças observadas, são apresentadas as propostas mecanísticas de cada método de reação para a formação de amidas N-alquilsubstituídas. Finalmente, as amidas sintetizadas foram avaliadas in vitro contra Fusarium oxysporum, mostrando atividade antifúngica em diferentes níveis (0.40 mM < IC50 < 29.1 mM), o que indica que as variações observadas na atividade desse grupo de compostos podem ser devidas ao efeito de amida acíclica como um bioisóstero não clássico de algumas fitoalexinas heterocíclicas.
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