Síntese e caracterização do 1, 2, 4 - oxadiázois 3, 5 - dissubistituidos que apresentam arquitetura molecular similar ao produto natural (R) - Goniotalamina.

Abstract

Oxadiazoles are five-membered heterocyclics that have a range of applications in the field of medicinal chemistry and materials. As, a (R)-Gonitalamine, some compounds containing the oxadiazole nucleus have good antiproliferative activity against a variety of strains of tumor cells. In this context, the central idea of ​​the work was the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles that have molecular architecture similar to (R)-Gonitalamine in order to obtain new structures with a high antiproliferative activity. For this, the synthetic strategy initially consisted in the esterification of (E)-cinnamic acid through catalysis, followed by synthesis of the aryl-amidoximes obtained from the reaction between the hydrochloride of hydroxylamine and the corresponding aryl nitriles. Once synthesized and characterized these intermediaries, the next step was the construction of the 1,2,4- 3,5-disubstituted oxadiazoles via the 0-acylamidoxime reaction followed of cyclodehydration using microwave oven as heating domestic. Additionally, the new 3,5-disubstituted 1,2,4-oxadiazoles were characterized by the usual spectrometric methods (IR and 1 H NMR and 13C). Ethyl (E)-cinnamate was obtained in 89% yield in the form of a viscous yellow liquid, while the aryl-amidoximes were obtained with yields ranging from 35 to 98% in reaction times from 2.3 to 78 hours. The 3,5-disubstituted 1,2,4-oxadiazoles obtained through microwave oven heating with short reaction times from 15 to 26 minutes and yields in the range of 12 to 66%.