Nous avons mis au point une réaction tandem couplage/cyclisation entre des dérivés acides carboxyliques ß-iodés et des alcynes vrais en présence sels de cuivre. Cette transformation conduit régio et stéréosélectivement à la formation de ?-alkylidènebuténolides. Les différents essais effectués ont montré que la méthodologie tolère un grand nombre de substrats et de fonctions. L’extension de la réactivité sur des acides carboxyliques a,ß-dihalogénés nous a permis d’accéder régio et stéréosélectivement à la formation d’a-halogéno-?-alkylidènebuténolides. La conservation d’un halogène sur le buténolide obtenu dénote la flexibilité de la transformation et permet ensuite d’étendre la structure du buténolide par les réactions de couplage croisés. Cette flexibilité nous a permis d’accéder à la synthèse de rétinoïdes et de précurseurs de nostoclides I et II. Une étude annexe sur des substrats de type aromatiques et hétéroaromatiques a montré l’invertion de la régiosélectivité au profit de la formation d’a-pyranone. Ces essais ont conduit à la synthétiser de nombreux indoles, isocoumarines et thiophènes originaux. / We have developed a tandem coupling/cyclization reaction between ß-iodided acrylic acid derivatives and true alkynes in the presence of copper salts. This transformation led regio and stereoselectively to the formation of ?-alkylidenebutenolides. Different tests have shown that the method tolerates many substrates and functions. The extension of the reactivity on a,ß-dihalogenated acrylic acids derivatives allowed us to access regio and stereoselectively to the formation of a-halo-?-alkylidenebutenolides. The conservation of a halogen on the butenolides obtained indicates the flexibility of the process and allows then the extention of the butenolide structure by cross-coupling reactions. This flexibility has allowed us to access to the synthesis of retinoids and nostoclides I and II precursors. An annex study on other substrates like aromatic and heteroaromatic systems showed the inversion of the regioselectivity of our methodology in favor of the formation of a-pyranone. These tests led to the synthesis of many original indoles, isocoumarines and thiophenes moieties

Made available in DSpace on 2015-03-26T13:00:03Z (GMT). No. of bitstreams: 1 texto completo.pdf: 802007 bytes, checksum: bcc020909e933a451dfda4bc8f17dee0 (MD5) Previous issue date: 2007-10-29 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The nostoclides belong to a class of natural compounds called γ-alkylidenebutenolides that have several representatives with biological application. To contribute to the study of this class of compounds, this present work aimed to synthesize new butenolides analogous to the nostoclides from furan-2 (5H)-one [8] and evaluate the phytotoxic activity of theses compounds on the development of sorghum and cucumber root growing. For the synthesis of the analogues to the nostoclides, the furan-2(5H)-one was converted in the compound 2-furyl-N,N,N',N'-tetraethyldiamide-phosphate that treated with 3-chlorobenzyl bromide resulted in the formation of the intermediary 3-(3-chlorobenzyl)furan-2(5H)-one [15]. The aldolic addition reaction between the lactone [15] and various aromatic aldehydes with subsequent elimination reaction provided the achievement of the following analogous to the nostoclides: (5Z)-3-(3-chlorobenzyl)-5-(3,4- methylenedioxybenzylidene)furan-2(5H)-one [17], (5Z)-3-(3- chlorobenzyl)-5-(4-fluorobenzylidene)furan-2(5H)one [18], (5Z)-3-(3-chlorobenzyl)-5-(4-bromobenzylidene)furan-2(5H)- one [19], (5Z)-3-(3-chlorobenzyl)-5-(2- bromobenzylidene)furan-2(5H)-one [20], (5Z)-3-(3-chlorobenzyl)-5-(4-trifluormethylbenzylidene)furan-2(5H)-one [21], (5Z)-3-(3-chlorobenzyl)-5-(2,5-dimethoxybenzylidene) furan-2(5H)-one [22], (5E)-3-(3-chlorobenzyl)-5-(2,4,6- trimethoxybenzylidene)furan-2(5H)-one [23], (5Z)-3-(3- chlorobenzyl)-5-(3-nitrobenzylidene)furan-2(5H)-one [24], (5Z)-3-(3-chlorobenzyl)-5-benzylidenefuran-2(5H)-one [25]. The nine news synthesized compounds were submitted to the evaluation of the herbicide activity, in concentrations of 10 and 100 ppm, using cucumber (Cucumis sativus) and sorghum (Sorghum bicolor) as test plants in Petri dishes. All the compounds were active, inhibiting the root system of the seeds of sorghum in two concentrations. By the statistical analysis, in the concentration of 10 ppm, the presence of substituents in the benzylidene group in the compounds [17], [18], [20], [22], [23] and [24] showed less herbicide activity than the compound [25], not replaced. The phytotoxic activity was not dependent on the presence of substituents groups in the compounds [19] and [21], since the results did not differ statistically between themselves, compared to the compound [25], not replaced. For the test using cucumber seeds, the compounds [17] and [23], in the concentration of 100 ppm, showed a contrary action, stimulating the root growth of that culture. The same behavior was observed for the compounds [23] and [24], in the concentration of 10 ppm. Among the tested substances, the one that showed greater inhibition to the sorghum culture was the compound [17] with percentage of inhibition of 70.7% (10 ppm) and 75.8% (100 ppm) and to the cucumber culture the compound [19] was the one that presented greater percentage of inhibition, 41.9% (10 ppm) and 41.1% (100 ppm). / Os nostoclídeos pertencem à classe de compostos naturais denominados γ-alquilidenobutenolídeos que possuem vários representantes com aplicação biológica. Para contribuir com o estudo dessa classe de compostos, este trabalho teve como objetivo sintetizar novos butenolídeos análogos aos nostoclídeos a partir da furan-2(5H)-ona [8] e avaliar a atividade fitotóxica desses compostos sobre o desenvolvimento radicular de sorgo e pepino. Para a síntese dos análogos aos nostoclídeos a furan-2(5H)-ona foi convertida no composto 2-furil-N,N,N ,N - tetraetildiamidofosfato que ao ser tratado com brometo de 3- clorobenzila resultou na formação do intermediário 3-(3- clorobenzil)furan-2(5H)-ona [15]. A reação de adição aldólica entre a lactona [15] e diferentes aldeídos aromáticos com posterior reação de eliminação proporcionou a obtenção dos seguintes análogos aos nostoclídeos: (5Z)-3-(3-clorobenzil)- 5-(3,4-metilenodi-oxibenzilideno)furan-2(5H)-ona [17], (5Z)- 3-(3-clorobenzil)-5-(4-fluorobenzili-deno)furan-2-(5H)ona [18], (5Z)-3-(3-clorobenzil)-5-(4-bromo-benzilideno)furan-2 (5H)-ona [19], (5Z)-3-(3-clorobenzil)-5-(2-bromobenzilideno) furan-2(5H)-ona [20], (5Z)-3-(3-clorobenzil)-5-(4- trifluorometilbenzilideno)furan-2(5H)-ona [21], (5Z)-3-(3- clorobenzil)-5-(2,5-dimetóxibenzilideno)furan-2(5H)-ona [22], (5E)-3-(3-clorobenzil)-5-(2,4,6-trimetóxibenzilideno) furan-2(5H)-ona [23], (5Z)-3-(3-clorobenzil)-5-(3- nitrobenzilide-no)furan-2(5H)-ona [24], (5Z)-3-(3- clorobenzil)-5-benzilidenofuran-2(5H)-ona [25]. Os nove novos compostos sintetizados foram submetidos à avaliação da atividade herbicida, nas concentrações de 10 e 100 ppm, utilizando como planta teste pepino (Cucumis sativus) e sorgo (Sorghum bicolor), em ensaio de Placa de Petri. Todos os compostos se mostraram ativos inibindo o sistema radicular das sementes de sorgo nas duas concentrações estudadas. Pela análise estatística, na concentração de 10 ppm, a presença de substituintes no grupo benzilideno para os compostos [17], [18], [20], [22], [23] e [24] conferiu uma diminuição da atividade herbicida em relação ao composto [25] não substituído. Já para os compostos [19] e [21] a atividade fititóxica não se mostrou dependente da presença dos grupos substituintes, uma vez que os resultados não diferem estatisticamente entre si, em relação ao composto [25] não substituído. Já para o ensaio utilizando sementes de pepino, os compostos [17] e [23], na concentração de 100 ppm, apresentaram ação contrária, estimulando o crescimento radicular dessa cultura. Esse mesmo comportamento foi observado para os compostos [23] e [24], na concentração de 10 ppm. Dentre as substâncias testadas, a que mostrou maior inibição frente à cultura de sorgo foi o composto [17] com porcentagem de inibição de 70,7% (10 ppm) e 75,8% (100 ppm) e para a cultura de pepino o composto [19] foi o que apresentou maior porcentagem de inibição, 41,9% (10 ppm) e 41,1% (100 ppm).