CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / The present work reports the chemical study related to the stem and the roots of Croton limae, collected in AndaraÃ/BA. The phytochemical investigation of ethanol extract from the stem lead to the isolation of two kaurane-type diterpenes, ent-kaur-16-en-18-oic acid and ent-kaur-16-en-15-oxo-18-oic acid, two clerodane-type diterpenes, 3,12-dioxo-15,16-epoxy-4α-hydroxycleroda-13(16),14-diene and 3-oxo-4α-hydroxy-13,14,15,16-tetranorclerodan-12-oic acid, and the flavonoid quercetin 3-O-β-D-glucopyranoside. The investigation of the hexane extract from the roots lead to the isolation of one triterpene, acetyl aleuritolic acid, the new dimer ent-17(α-pinen-10â-yl)-15-oxokauran-18-oic acid, two news clerodane diterpenes, 3-oxo-15,16-epoxy-4α,12-dihydroxycleroda-13(16),14-diene and 15,16-epoxy-3α,4α,12-trihydroxycleroda-13(16),14-diene, one halimane-type diterpene, 15,16-epoxy-3α,12-dihydroxyhalima-5(10),13(16),14-triene and the mixture of steroids β-sitosterol and stigmasterol. From the ethanol extract of the roots, it was possible to isolate the flavonoids kaempferol 3-O-β-glucopyranoside and ombuine 3-O-β-rutinoside and the three new clerodane diterpenes 3α,4α,15,16-tetrahydroxyclerod-13-ene, 6-(β-D-glucopyranosyl)-3,12-dioxo-15,16-epoxi-4α-hydroxycleroda-13(16),14-dieno and 3-oxo-4α,12-dihydroxy-14,15,16-trinorclerodan-13-oic acid. Four aromatic derivatives amides from ent-kaur-16-en-18-oic acid were prepared through nucleophilic substitutive reactions. The corresponding methyl esters from the ent-kaur-16-en-18-oic acid and ent-kaur-16-en-15-oxo-18-oic acid were also obtained. Two new derivatives from 3,12-dioxo-15,16-epoxi-4α-hidroxicleroda-13(16),14-dieno were prepared through reduction reaction and another one by the biotransformation of diterpene, made by the fungus Rhizopus stolonifer. Some isolated compounds and derivatives were submited to cytotoxic activity using ovarian (OVCAR-8), glioblastoma (SF-295) and colon (HCT-116) cell lines, and the compounds ent-kaur-16-en-15-oxo-18-oic acid and ent-17(α-pinen-10â-yl)-15-oxokauran-18-oic acid registered activity during preliminaries assays. The secondary metabolites were isolated through usual chromatography techniques, using thin layer chromatography, column chromatography, size exclusion chromatography and high performance liquid chromatography. The determination of the structure of the isolated compounds was performed through physical (melting point and optical rotation) and spectrometric techniques, such infrared (IR), high resolution mass spectrometry and nuclear magnetic resonance (NMR), including bidimensional experiments, and comparison with literature data. / O presente trabalho relata o estudo quÃmico do caule e das raÃzes de Croton limae, coletado no municÃpio de AndaraÃ-BA. A investigaÃÃo fitoquÃmica do extrato etanÃlico do caule levou ao isolamento de dois diterpenos do tipo caurano, Ãcido ent-caur-16-en-18-oico e Ãcido ent-caur-16-en-15-oxo-18-oico, dois diterpenos do tipo clerodano, 3,12-dioxo-15,16-epoxi-4α-hidroxicleroda-13(16),14-dieno e Ãcido 3-oxo-4α-hidroxi-13,14,15,16-tetranorclerodan-12-oico, e do flavonoide 3-O-β-D-glicopiranosilquercetina. A investigaÃÃo do extrato hexÃnico das raÃzes levou ao isolamento de um triterpeno, Ãcido acetilaleuritÃlico, do dÃmero inÃdito Ãcido ent-17(α-pinen-10â-il)-15-oxocauran-18-oico, de dois novos diterpenos clerodanos, 3-oxo-15,16-epoxi-4α,12-dihidroxicleroda-13(16),14-dieno e 15,16-epoxi-3α,4α,12-trihidroxicleroda-13(16),14-dieno, um diterpeno do tipo halimano, 15,16-epoxi-3α,12-dihidroxihalima-5(10),13(16),14-trieno, e da mistura dos esteroides β-sitosterol e estigmasterol. Do extrato etanÃlico das raÃzes foram isolados dois flavonoides, 3-O-β-D-glicopiranosilcanferol e ombuina-3-O-β-rutinosÃdeo, e trÃs diterpenos clerodanos inÃditos, 3α,4α,15,16-tetrahidroxicleroda-13-eno, 6-(β-D-glicopiranosil)-3,12-dioxo-15,16-epoxi-4α-hidroxicleroda-13(16),14-dieno e Ãcido 3-oxo-4α,12-dihidroxi-14,15,16-trinorclerodan-13-oico. Foram preparadas quatro amidas aromÃticas derivadas do Ãcido ent-caur-16-en-18-oico e os respectivos Ãsteres metÃlicos dos Ãcidos ent-caur-16-en-18-oico e ent-caur-16-en-15-oxo-18-oico. Foram preparados dois derivados reacionais obtidos atravÃs de reaÃÃes de reduÃÃo do diterpeno clerodano 3,12-dioxo-15,16-epoxi-4α-hidroxicleroda-13(16),14-dieno e outro atravÃs da biotransformaÃÃo deste diterpeno pelo fungo Rhizopus stolonifer. Alguns compostos isolados e derivados foram submetidos a testes de atividade citotÃxica, utilizando linhagens de cÃlulas tumorais de ovÃrio (OVCAR-8), glioblastoma (SF-295) e colÃn (HCT-116), onde testes preliminares indicaram que os compostos ent-caur-16-en-15-oxo-18-oico e Ãcido ent-17(α-pinen-10â-il)-15-oxocauran-18-oico apresentaram atividade. Os metabÃlitos secundÃrios foram isolados atravÃs de tÃcnicas cromatogrÃficas usuais, utilizando cromatografia em camada delgada, cromatografia em coluna, cromatografia por exclusÃo molecular e cromatografia lÃquida de alta eficiÃncia. A determinaÃÃo estrutural foi realizada atravÃs de mÃtodos fÃsicos (ponto de fusÃo e rotaÃÃo Ãptica) e do uso de tÃcnicas espectroscÃpicas e espectromÃtricas como infravermelho (IV), espectrometria de massas de alta resoluÃÃo e ressonÃncia magnÃtica nuclear de hidrogÃnio (RMN 1H) e carbono-13 (RMN 13C), incluindo experimentos bidimensionais, alÃm de comparaÃÃo com dados da literatura.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:9557 |
| Date | 22 August 2014 |
| Creators | Antonio HonÃrio de Sousa |
| Contributors | Mary Anne Sousa Lima, Francisco Geraldo Barbosa, Francisco Josà Queiroz Monte, Selene Maia de Morais, Maria Rose Jane Ribeiro Albuquerque |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em QuÃmica, UFC, BR |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
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