Síntese e avaliação da atividade fitotóxica de compostos heteroaromáticos análogos aos nostoclídeos

• Autor(a) principal: Varejão, Jodieh Oliveira Santana
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: LOCUS Repositório Institucional da UFV
• Texto Completo: http://locus.ufv.br/handle/123456789/2098
• topic: Herbicida; Nostoclídeos; Gama-alquinidenobutenolídeo; Herbicide; Nostoclides; Gama-alquinidenobutenolídeo; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA

Nostoclide I and II were isolated from a blue-green alga Nostoc sp, a constituent of the lichen Peltigera canina. These compounds are structurally similar to cianobacterina, a phytotoxic compound capable of inhibiting electron transport in photosystem II of photosynthesis. Some analogues to nostoclide also presented phytotoxic effects, inhibiting electron transport in the Hill reaction. Given the phytotoxicity of these compounds, the aim of the work here presented was to synthesize new heteroaromatics compounds analogues to nostoclide and evaluate the inhibitory effects of these compounds in the Hill reaction. For the synthesis of analogues to nostoclide, furfural was used as the starting material. The reaction of furfural with hydrogen peroxide and formic acid and subsequently with the N,N-diethylethanolamine led to the formation of lactone furan-2(5H)-one (47%). This lactone was reacted with phosphoryl chloride and triethylamine to form the compound furan-2-ylphosphoro dichloridate, which was not isolated. Reacting the latter with diethylamine lead to the formation of furan-2-yl N,N,N',N'- tetraethyldiamidophosphate (49%). The reaction of furyl with BuLi generated in situ the organolithium, wich was traped with benzyl bromide, yielding the substance 3-benzylfuran-2-yl N,N,N ,N'- tetraethyldiamidophosphate, wich was not isolated. The subsequent reaction of this substance with formic acid resulted in the 3- benzylfuran-2(5H)-one (66%). This lactone was subjected to aldol addition reaction with various furan derivatives. Further processing of the aldol adducts with DBU under reflux lead to the compounds analogues to nostoclide. The compounds 3-benzyl-5-((5-pclorophenyl) furan-2-ylmethylene)furan-2(5H)-one (87%), 3-benzyl-5-((5-o-nitro phenyl)furan-2-ylmethylene)furan-2(5H)-one (48%), 3-benzyl-5- ((5-p-bromo phenyl)furan-2-ylmethylene)furan-2(5H)-one (99%), (Z)-3-benzyl-5-((5-methyl) furan-2-ylmethylene)furan- (5H)-one (67%) and (Z)-3-benzyl-5-((5-ethyl)furan- 2-ylmethylene)furan-2(5H)-one (62%) were obtained as mixture of isomers in the ratio of Z:E, 58:42, 63:37, 69:31, 87:13, 30:70, respectively. These compounds isomerize in the presence of traces of acid. Was also synthesized compound (Z)-3-benzyl-5-(furan-2-ylmethylene)furan-2(5H)-one (58%). According to DFT calculations, compounds in Z configuration are more stable than their isomers. The synthesized compounds were subjected to biological tests to evaluate their inhibitory activity in the Hill reaction. The most active one was (Z)-3-benzyl-5-(furan-2-ylmethylene)furan-2(5H)-one (ID50 = 26.8 ± 1.7 μM).