Planejamento sintético e avaliação antitumoral de carboidratos enônicos.

Abstract

Sugars are the most abundant macromolecules of the earth, and it is estimated that about 70% of all biomass consists of sugars. Among the different types of sugars a class that stands out is the glycosides. The glycosides present numerous biological and technological applications, in addition to being versatile synthons applied in synthetic chemistry, because of these features and other functions, the objective of this work was synthesize, characterize and evaluate the antitumor activity of enones sugars obtained from successive transformations of D-glucose. In this sense, the methodology consisted of synthesizing tri-O-acetyl-D-glucal from the D-glucose, then promote the glycosidation reaction, followed by hydrolysis reaction and the oxidation reaction. All oxidation reaction products were subjected to anti-tumor activity against four strains of human tumor cells, which were, NCI-H292 (lung carcinoma), MCF (breast cancer), HEP (cervical carcinoma) and HL60 (promyelocytic leukemia). As a result tri-O-acetyl-D-glucal was obtained as an amorphous white solid in 90% yield. The glycosidation reaction by Ferrier rearrangement with different alcohols led to the 2,3-unsaturated O-glycosides with yields ranging from 89-95% in reaction times of 45-80 minutes. Basic hydrolysis of 2,3-unsaturated O-glycosides led to their hydrolysates O-glycosides in a yield varying from 85-98% quickly and selectively. The oxidation reaction using manganese dioxide of hydrolyzed O-glycosides led to enones sugars excellent yields 85-92% in reaction times which do not exceed 3 h. All synthesized compounds were characterized by different spectrometric techniques (IR, 1H and 13C NMR) and enones sugars were highly cytotoxic activity against the four cell lines tested showing IC50 ranging from 1.0 to 5.6 g/mL. These results demonstrate the efficiency of the methodologies used in the synthesis of enones sugars that have promising antitumor activity.