Síntese de novos adutos de Morita-Baylis-Hillman com potencial atividade biológica.

Abstract

This work was designed using the concept of classical bioisosterism where isoelectronic OH groups were replaced by the CH3 group, aimed at finding a relationship between the lipossolubility of the adducts Morita-Baylis-Hillman (AMBH) and its biological activity. Was developed in this work, synthetic methodologies for the preparation of 16 AMBH unprecedented (47-62), getting good and high yields and moderate reaction times. Initially was synthesized AMBH 8 using the 2-hydroxyethyl Acrylate 45 as Michael acceptor, giving the adducts 47 (2-hydroxyethyl [2-(hy-droxy(2-nitrophenyl)methyl)] acrylate, 71%), 48 (2-hydroxyethyl [2-(hydro- xy(3-nitrophenyl)methyl)] acrylate, 50%), 49 (2-hydroxyethyl [2-(hydroxy(4-nitrophenyl)methyl)] acrylate, 62%), 50 (2-hydroxyethyl [2-(hydroxy(pyridin-2-yl)methyl)] acrylate, 94%), 51 (2-hydroxyethyl [2-(hydroxy(pyridin-3-yl) methyl)] acrylate, 83%), 52 (2-hydroxyethyl [2-(hydroxy(pyridin-4-yl)methyl)] acrylate, 80%), 53 (2-hydroxyethyl [2-((4-bromophenyl)(hydroxy)methyl)] acrylate, 67%), 54 (2-hydroxyethyl[2-(hydroxy(naphthalen-2-yl)methyl)] acrylate, 71%). The second step ofthe synthesis was the preparation of Propyl Acrylate (46), from acrylicacid and propanol (yield 98%), which was later used as Michael acceptorsin the synthesis of AMBH 55 (Propyl [2-(hydroxy(2-nitro-phenyl)methyl)]acrylate, 68%), 56 (Propyl [2-(hydroxy(3-nitrophenyl)methyl)] acrylate, 73%), 57 (Propyl [2-(hydroxy(4-nitrophenyl)methyl)] acrylate, 97%), 58 (Propyl [2-(hydroxy(pyridin-2-yl)methyl)]acrylate, 70%), 59 (Propyl [2-(hydroxy(pyridin-3-yl)methyl)acrylate], 80%), 60 (Propyl [2-(hydroxy(pyridin-4-yl)methyl)] acrylate, 66%), 61 (Propyl [2-((4-bromophenyl)(hydroxy)methyl)] acrylate, 64%), 62 (Propyl [2-(hydroxy(naphthalen-2-yl)methyl)] acrylate, 60%).