Síntese e caracterização de novos adutos de Morita-Baylis-Hillman (AMBH) homodiméricos com potencial atividade anticâncer

Abstract

In view of the promising bioactivity that the Morita-Baylis-Hillman adducts (AMBH) have presented as potential drug candidates and the possibility of developing new compounds belonging to this class with anticancer activity, this paper aims to synthesize and characterize new AMBH according to twin drugs approach, since the structures obtained have two identical pharmacophoric groups covalently linked by a spacer, in this case being called homodimers. The homodimeric compounds were obtained from the reaction between 1,3-propanediol diacrylate 28 with six aromatic aldehydes. First the preparation of the diacrylate was carried out by Fischer's esterification reaction between 1,3-propanediol 30 and acrylic acid 29, which was obtained in 61% yield. The homodimers 22-27 were synthesized by reaction between diacrylate 28 with the aldehydes 2-nitrobenzaldehyde 31, 3-nitrobezaldeído 32, 4-nitrobenzaldehyde 33, 4-bromobenzaldehyde 34, 4-chlorobenzaldehyde 35 and 4-fluorbenzaldehyde 36, using DABCO as catalyst and acetonitrile as solvent. All the reactions studied occurred in moderate to good yields (35-70%) leading to the formation of both homodimers and monosubstituted products 22a - 27a. The products were purified by flash chromatography and characterized by Infrared and Nuclear Magnetic Resonance spectroscopy.