Síntese de novos derivados halogenados da bergenina para o estudo de reações via acoplamento mediado por paládio.

Abstract

Bergenin is a C-glycoside of 4-O-methylgallic acid isolated from several plant species around the world, especially those of the Humiriaceae family. In the Amazon region, Endopleura uchi stands out, from which the substance can be isolated from the bark of the stem. Due to the biological effectiveness of bergenin, an opportunity arises to make structural modifications based on its basic structure, aiming at the production of derivatives that have equal or better performance in biological activities. This approach can be achieved through semisynthesis. Seeking to produce novel amphiphilic structures derived from bergenin to perform biological studies, the present study aimed to insert hydrophobic groups into the aromatic ring of bergenin, specifically via palladium-mediated couplings as the main strategy for C–C bond formation. To achieve this goal, the synthetic route consisted of halogenation of the aromatic ring of bergenin, followed by a step of protection of the hydroxyls of the structure for subsequent carry out the coupling reactions. The chlorination and bromination reactions were successfully performed, as well as the acetylation of these products occurred with good yields, producing three new molecules. Heck coupling reactions were attempted between the halogenated products and the alkenes isobutylene and citronellal, Sonogashira cross-coupling between the same products and propargyl alcohol, and also Negishi coupling using bromohexane, but all three couplings were unsuccessful. In addition to these results, the halogenated products with and without free hydroxyls were evaluated for their cytotoxic potential on leukemia cell lines, having presented moderate results of cytotoxic activity. We conclude that the synthetic route tested in this work is promising in providing halogenated derivatives of bergenin, however the coupling reactions require adjustments, such as the use of alternative palladium complexes and coupling substrates to those used in this work.