Orientador: Lauro Euclides Soares Barata / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-14T13:59:26Z (GMT). No. of bitstreams: 1 Aveniente_Mario_M.pdf: 13424505 bytes, checksum: f5e9cb10d6b222148cc1a7cd555a98dc (MD5) Previous issue date: 2009 / Resumo: Neolignanas e lignanas são substâncias importantes, devido suas atividades biológicas e farmacológicas. Quimicamente, lignanas são dímeros resultantes do acoplamento oxidativo do ácido cinâmico e/ou álcool cinamílico, e neolignanas derivadas de alil e/ou propenil fenóis. Nesta dissertação, as sínteses de neolignanas e análogos resultaram das reações de condensação de intermediários a-bromocetonas com fenóis e tiofenóis. Reações de oxidação no enxofre de alguns análogos de neolignanas foram feitas para a obtenção dos derivados sulfóxido e sulfonas, usando ácido m-cloroperbenzóico e ácido peracético. Neolignanas-alcoóis foram obtidas via reações de redução com NaBH4, e o respectivo derivado acetato através da reação de acetilação com anidrido acético e piridina. Os análogos quirais foram obtidos da reação de cetonas aquirais com (d) e (l)-dimetil tartarato, proporcionando cetonas quirais que reagiram em seguida com bromo resultando em a-bromocetonas quirais e estas com derivados de tiofenóis, levando à quatro análogos quirais. Em pesquisas anteriores nosso grupo realizou ensaios biológicos de neolignanas e análogos em Leishmania donovani, tendo sido verificado que os análogos sulfurados apresentavam maior atividade anti-leishmania. Então, vinte e oito análogos de neolignanas sintéticos contendo S e O na ponte C-8 foram obtidos neste projeto de mestrado, sendo vinte e quatro compostos racêmicos e quatro compostos quirais. Em cooperação com o Instituto Carlos Chagas- UFRJ os vinte e oito análogos de neolignanas sintéticos foram testados in vitro em Leishmania donovani e L. amazonensis. Os resultados mostraram que quatro substâncias, dois racêmicos e seus respectivos análogos quirais, produziram significativas atividades anti-leishmania. / Abstract: Neolignans and lignans present significant biological and pharmacological activities. Chemically lignans are dimers derived from the oxidative coupling of cinnamic and/or cinnamyl alcohol, while neolignans derive from allyl and/or propenyl phenols. In this work, the synthesis of neolignans and correlated substances resulted from the condensation reactions between intermediate alpha-bromoketones with phenols and thiophenols. Sulphur oxidation reactions of certain neolignans analogues leading to neolignans-sulfoxide and sulfones respectively were also carried out, with the use of m-chloroperbenzoic and peracetic acids. Neolignans-alcohols were obtained using NaBH4 reductions while its acetate derivative was obtained from the acetylation reaction, with acetic anhydride and pyridine. The chiral reactions started with non-chiral ketones, which reacted with d/l-dimethyl-tartrate, providing chiral ketones that reacted with bromine, resulting in chiral a-bromoketone, these in their turn reacted with thiophenols leading to four chiral analogues. In previous studies conducted by our group, neolignans carrying oxygen and sulphur on the C-8 were essayed in Leishmania donovani showing that sulphur-neolignans had significant anti-leishmania activity. From the twenty-eight synthetic neolignans analogues containing O and S on the C-8 bridge obtained in this Master in Science project, twenty-four were racemic and four were chiral compounds. In cooperation with the UFRJ Carlos Chagas Institute, all substances were tested in vitro in Leishmania donovani and L. amazonensis. The results showed that four substances, two racemic and their respective chiral analogues, had significant anti-leishmania activity. / Mestrado / Quimica Organica / Mestre em Química

Orientador: Paulo Jose Samenho Moran / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-15T03:11:12Z (GMT). No. of bitstreams: 1 Martins_RodrigodosSantos_M.pdf: 9288307 bytes, checksum: f6f89494491cb3965ccd1e83f1ff7920 (MD5) Previous issue date: 2009 / Resumo: Em estudos recentes, o racemato da 2-(4-clorofeniltio)-1-(3,4-dimetoxifenil)-1- propanona (15b), molécula análoga sintética das neolignanas isoladas da Virola surinamensis, apresentaram atividade anti-leismania. Neste trabalho com o objetivo de sintetizar 15b opticamente pura, obtivemos (2S)-2-hidroxi-1-(3,4-dimetoxifenil)-1- propanona (2c) através da biorredução da 1-(3,4-dimetoxifenil)-1,2-propanodiona (1c) mediada pelo fermento de pão (Saccharomyces cerevisiae) com 60% de rendimento e 93% de e.e. Consecutivamente testou-se uma série de protocolos para a realização de uma SN2 entre 2c e o p-clorotiofenol para a síntese de 15b enantiomericamente pura. A transformação do grupo hidroxila de (+)-(2S)-2c em um éster sulfônico seguida da substituição via catálise por transferência de fase (CTF) provou ser a melhor estratégia na obtenção de 15b. Ao fim do trabalho se sintetizou ambos os enantiômeros de 15b, a (-)-15b com 10% de rendimento e 95% de e.e., a partir do éster sulfônico de 2c, e a (+)-15b com 90% de rendimento e 60% de e.e. partindo-se da (-)-2-cloro-1-(3,4-dimetoxifenil)-1- propanona, um co-produto da síntese do éster sulfônico de 2c. Conjuntamente, estudou-se uma metodologia alternativa na obtenção de 2-hidroxi-1-aril-1-propanona (2) através da resolução cinética de fenilpropanodiois, realizada por meio de uma oxidação biocatalítica mediada pelo fermento de pão. Após a otimização de alguns parâmetros reacionais, partindo-se do (±)-anti-1-fenil-1,2-propanodiol (4a), se obteve a (2S)-2-hidroxi-1-fenil-1-propanona (2a) com 25% de rendimento e 83% de e.e. e a (1S,2R)- 4a com 30% de rendimento e 68% de e.e. depois de 7 dias de reação. O mesmo procedimento foi realizado com outros microrganismos, com destaque para o resultado da bioxidação mediada pelo Geotrichum candidum, onde se obteve somente a (1S,2R)-4a com 30% de rendimento e 99% de e.e. após 5 dias de reação. / Abstract: Recently, the racemate 2-(4-chlorophenylthio)-1-(3,4-dimethoxyphenyl)-1- propanone (15b) that is an analog synthetic of neolignans, isolated from Virola surinamensis shows anti-leismania activity. In this work, we performed the bioreduction of 1-(3,4-dimethoxy)1,2-propanodione (1c) mediated by baker yeast (Saccharomyces cerevisiae) affording (2S)-2-hydroxy-1-(3,4-dimethoxyphenyl)-1-propanone (2c) in 60% yield and 93% e.e. which is an intermediate for 15b. Consecutively, protocols were applied to perform SN2 reaction of 2c and p-chlorotiophenol in order to synthesize optically pure 15b. The reaction of sulfonic ester of (+)-(2S)-2c with p-chlorotiophenol catalyzed by phase transfer catalysis (PTC) shows to be a better strategy to obtain 15b. Both enantiomers of 15b were synthesized, (-)-15b was obtained in 10% yield and >95% e.e. from sulfonic ester from 2c, and (+)-15b was obtained in 90% yield and 60% e.e. from (-)-2-chloro-1- (3,4-dimethoxyphenyl)-1-propanone that was a by-product formed in the synthesis of sulfonic ester from 2c. In addition, an alternative methodology for obtaining 2-hydroxy-1-aryl-1-propanone (2) was applied through kinetic resolution of 1-phenylpropane-1,2-propanediol by biocatalytic oxidation mediated by bakers yeast. After optimization of this process, the (2S)-2-hydroxy-1-phenyl-1-propanone (2a) and (1S,2R)-4a were obtained in 25% yield and 83% e.e. and 30% yield and 68% e.e. respectively from (±)-anti-1-phenyl-1,2-propanediol (anti-4a) after 7 days. The same protocol was applied with other microorganisms as Geotrichum candidum that produced (1S,2R)-4a in 30% yield and 99% e.e. after 5 days. / Mestrado / Quimica Organica / Mestre em Química

Este trabalho descreve os isolamentos e as determinações estruturais dos metabólitos secundários das diferentes partes dos frutos (pericarpos, arilos, tegumentos e amêndoas) de Virola elongata. 0 material foi coletado em Humaitá (AM) e no Km 96 da Rodovia Santarém-Cuiabá (PA). Os constituíntes químicos foram isolados por cromatografias de adsorção e tiveram suas estruturas identificadas ou determinadas por técnicas espectrométricas usuais (IV, UV, RMN e EM). As configurações absolutas dos metabólitos foram deduzidas a partir de medidas espectropolarimétricas, ou auxiliadas pela obtenção de derivados mais informativos. As substâncias foram agrupadas nas seguintes subclasses: lignanas furofurânicas [(+)-sesamina (LF-1), (+)-epifargesina (LF-2), (+)-eudesmina (LF-3), (+)-fargesina (LF-4), (+)-filigenina (LF-5) e (+)-epieudesmina (LF-6)]; lignanas tetraidrofurânicas [(+)-magnostelina-A (LT-1), (+)-magnostelina-C (LT-2), (±)-4\'-metil-5\'-metoxi-lariciresinol (LT-3), (±)-4,4\'-dimetil-5\'- metoxi-lariciresinol (LT-4) e (±)-4-4\'-dimetil-5\'-hidroxi-5-metoxi-lariciresinol (LT-5)]; Lignana diarilbutanólica [(-)-4,4\'-dimetil-5-metoxi-secolariciresinol (LD-1)]; e lignanas dibenzilbutirolactâmicas [(-)-hinokinina (DB-1), (-)-kusunokinina (DB-2), (-)-dimetilmatairesinol (DB-3), (-)-metiltujaplicatina (DB-4), (-)-dimetil-5-hidroximatairesinol (DB-5) e (-)-dimetil-5-metoxi-matairesinol (DB-6)]; neolignanas diarilbutânicas [ND-1, ND-2 e ND-3], neolignana ariltetralínica: galbulina (NA-1) e neolignanas ariltetralônicas [(-) e (+)-oxoisogalcatina (NA-2), (+)-hidroxi-isogalcatina (NA-3), diidroxi-oxoisogalcatinas epiméricas inéditas (NA-4 e NA-5), NA-6, NA-7, (+)-otobanona (NA-8), hidroxi-otobanonas epiméricas (NA-9 e NA-10)]; neolignanas secoariltetralínicas (ND-5 e seu acetato ND-6]; uma neolignana dimérica [NA-11] e ainda diversos policetídeos acilresorcinólicos e acifloroglucinôlicos [AR-1 a AR-8]. 0 padrão 3,4-dioxigenado nos anéis aromáticos é predominante na maioria dos lignóides isolados. 0 padrão 3,4,5-trioxigenado observado nos anéis aromáticos de lignanas dibenzilbutirolactônicas (DB-4 e DB-5), diarilbutanólica (LD-1) e tetraidrofurânicas (LT-3, LT-4 e LT-5) e, o padrão 2,4,5-trioxigenado observado para neolionanas ariltetralônicas (NA-6, NA-7), conferem para algumas o caráter inédito. A maior variação no padrão de substituição de esqueletos foi observada para neolignanas ariltetralônicas, o que motivou a elaboração de experimentos especíificos em RMN- 1H (ENO e uso de reagente de deslocamento) associados a análise dos dados de RMN- 13C para proposições de constituições e de configurações relativas. Foi constatada a presença das neolionanas NA-2, NA-9 e NA-10 nos extratos dos tegumentos e de seus enantiômeros nos extratos das amêndoas de V. elongata (PA). Algumas classes de substâncias isoladas foram correlacionadas biossinteticamente a partir de suas configurações absolutas. A quantificação aproximada das substâncias identificadas foi efetuada, através das quantidades isoladas e análises de espectros de RMN-1H de frações impuras. Nos pericarpos e arilos foi constatada a presença exclusiva e alternada de lignanas furofurâanicas e lignanas dibenzilbutirolactônicas entre os frutos de diferentes localidades. Essas lignanas, também presentes nos tegumentos, ocorrem em maior teor com maior diversidade de substituição nos anéis aromáticos, mas são completamente ausentes nos extratos das amêndoas, onde o perfil é baseado na presença de neolignanas ariltetralônicas e policetídeos. Os policetídeos com anéis aromáticos di- e triidroxilados foram isolados, principalmente, dos tegumentos e amêndoas. A análise do extrato de uma das amêndoas foi baseada na análise conjunta do espectro de RMN-1H, dos cromatogramas em camada delgada e dos dados obtidos por cromatografia gasosa acoplada a espectrometria de massas. A metodologia foi tentativamente aplicada á análise das diversas partes dos frutos de V. sebifera coletada em Roraima. Os dados obtidos sobre as estruturas e distribuição dos metabólitos são confrontados com os descritos na literatura para espécies taxonomicamente afins. / This work describes isolations and structural determinations of secondary metabolites in parts of fruits (pericarps, arils, teguments and kernels) from Virola elongata. Material was collected in Humaita (AM) and Km 96 of Santarém-Cuiabá Road (PA). The chemical constituents were isolated by chromatographic processes and their structures identified or elucidated by usual spectrometric techniques (IR, UV, NMR, and MS). Absolute configuration were deduced through spectropolarimetric measures, or based on data from derivatives. The compounds were classified in the following classes: furofuran lignans [(+)-sesamin (LF-1), (+)-epifargesin (LF-2), (+)-eudesmin (LF-3), (+)- fargesin (LF-4), (+)-phylligenin (LF-5) and (+)-epieudesmin (LF-6)]; tetrahydrofuran lignans [(+)-magnostelin-A (LT-1), (+)-magnostelin-C (LT-2), (±)-5\'-methox y -4\'-methyl-lariciresinol (LT-3), (±)-5\'-methoxy-4,4\'-dimethyl-lariciresinol (LT-4) and (±)-5\'-hydroxy-5-methoxy-4,4\'-dimethvl-lariciresinol (LT-5)]; diarylbutanol lignan [(-)-4,4\'-dimethvl-5-methoxy-secolariciresinol (LD-1)]; and dibenzylbutyrolactone lignans [(-)-hinokinin (DB-1), (-)-kusunokinin (DB-2), (-)-dimethylmatairesinol (DB-3), (-)-methylthujaplicatin (DB-4)]; diarylbutane neolignans (ND-1, ND-2 and ND-3); aryltetralin neolignans [galbulin (NA-1) and aryltetralone neolignans [(-)- and (+)-oxoisogalcatin (NA-2), (+)-hydroxyisogalcatin (NA-3), unpublished epimeric dihydroxy-isogalcatins (NA-4 and NA-5), (+)-otobanone (NA-8), epimeric hydroxy-otobanones (NA-9 and NA-10)]; secoaryltetralin neolignans [ND-5 and its acetate (NA-6).1; dimeric neolignan (NA-11) and several acylresorcinol and acylphloroglucinol polyketides (AR-1 to AR-8). The 3,4-dioxygenated pattern was observed in aromatic rings of the majority isolated lignans. The 3,4,5-trioxygenated pattern observed in dibenz y lbutyrolactone lignans (DB-4 e DB-5), diarylbutanol (LD-1), and tetrahydrofuran lignans (LT-3, LT-4, LT-5), and the 2,4,5-pattern observed in aryltetralone neolignans, confer to some of them the unusual character. The main variation in the substitution pattern was observed in aryltetralone neolignans, which needed more detailed study involving 1H-NMR experiments (NOE and LIS reagent) and refined analysis of 13C-NMR data. It was observed the presence of NA-2, NA-9 and NA-10 neolignans in teguments and its enantiomers in kernels of fruits from Virola elongata (PA). The biosynthetic relationships among several classes of lignoids are discussed under their absolute configurations. The near concentration of identified compounds was obtained from isolated quantities and analysis of 1H-NMR spectra of mixtures. In pericarps and arils was determined the exclusive and alternated presence of furofuran and dibenzylbutyrolactone lignans between fruits from different localities. These last two subclasses, also present in teguments, occur in higher concentrations and substitution diversifications in aromatic rings, but are completely absent in kernels whose profile is based on the presence of aryltetralone lignans. The poliketide with di- and trihydroxylated aromatic rings were isolated mainly from teguments and kernels. The analysis from kernels extract was performed by combined analysis involving 1H-NMR spectra, thin layer chromatography, and gas chromatography coupled to mass spectrometry. This methodology was tested to analyse the parts of fruits from Virola sebifera collected in Roraima. The obtained informations about structures of metabolites and their distributions in fruits was compared with those data described for taxonomically closed species.

Made available in DSpace on 2015-04-22T22:02:15Z (GMT). No. of bitstreams: 1 Orivaldo da Silva Lacerda Junior.pdf: 1992169 bytes, checksum: a6dc8eb601838e7cd5ab6683fbae3529 (MD5) Previous issue date: 2009-02-20 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The virola surinamensis Rott Warb is a kind of family Myristicaceae exploited because of their timber. This study sought to describe the fat extracted from its seed, part renewable, abundant and inexpensive operated the plant, whose operation can reconcile environmental preservation, sustainable regional development to improvement of life of local people. Seeds collected and drawn by mechanical pressing in the Community of Roque located in the extractive Reserve Jurua results in yellowing of fat dark. The contents of that fat physical and chemical methods were obtained from official and presented with characteristic of high acidity and a high amount of material unsaponifiables were made different tests for separation of unsaponifiable and neutralization of that fat in the laboratory. The fat was subjected to an extraction of the material unsaponifiables by a process of partition net-net for 4 hours at 80 °C, followed by neutralization with alkaline solution. After the optimization of this process, the material was extracted unsaponifiable on a larger scale with different proportions of alcohol (methanol, ethanol and absolute ethanol) with the best result the extraction with methanol 1:2 fat / methanol). That fraction of unsaponifiable extracted with methanol was subjected to a phytochemical isolation by different chromatographic techniques. There were isolated six substances, which were characterized by Nuclear Magnetic Resonance technique using mono-(1H and 13C NMR) and two-dimensional (COSY, HSQC and HMBC). 4 have been identified neolignanas the mesodihidroguaiarético, hidroxigalbolina, f23/mpmi, f12/14/18 two lactones and the type jurenolido C. The trials of antioxidant activities qualitative indicated that all substances isolated present capacity of kidnapping of free radicals. After filtering the fat, with higher rate of acidity, was subjected to a transesterification by acid homogeneous catalysis with different proportions of catalyst, through metílica. The yield reached in a single step was 58.6 % in the following conditions (fat / methanol 1:6, 1 M HCl, and temperature 90 ° C in 24 hours), this result was lower than expected for catalysis acid that is above 90 % Due to presence of material unsaponifiables in fat. The fat that has also been neutralised and submitted through the transesterification metílica and etílica relations in different molars by basic homogeneous catalysis (KOH, and EtONa NaOH), in different proportions. He had his best results seen with higher incomes, density and conversion to CCD was 90, 01 % under the following conditions (fat / methanol 1:9; KOH 2% and temperature of 50 °C in 2 hours), for basic catalysis was obtained 81.68 % (Fat / absolute ethanol 1:12; KOH 4% and temperature of 80 °C in 2h), 86.81 % (fat / absolute ethanol 1:6, 2% NaOH and temperature of 60 xviii °C in 2horas) and 82.81 % (fat-ethanol absolute 1:6, EtONa 2% and temperature of 80 °C in 2horas). With the best result the transesterification with the basic catalyst NaOH. The crude fat and fat white material obtained from the unsaponifiable with high acidity was subjected to an esterification with heterogeneous catalysts (FeCl3 and Fe2(SO4)3), followed by transesterification in catalysis basic to obtain biodiesel. Thus the following results were obtained 90.74% under the (esterification Fe2(SO4)3 2 %; fat / 1:3 ethanol and temperature of 90 °C in 4 hours and transesterification KOH 2 %, fat / 1:12 ethanol and temperature of 80 °C in 2 hours), cited in the hydrolysis was found better yield of 96.53% in terms of (NaOH 4%, fat / 1:3 absolute ethanol and temperature of 90 °C in 1 hour and esterification fat / absolute ethanol 1: 3; Fe2(SO4)3 2% to 90 °C in 2 hours). The optimization of the process of preparation of biodiesel, from the fat of ucuúba may provide a new source of energy to the isolated communities of the State of Amazonas. / A Virola surinamensis Rott Warb é uma espécie da família Myristicaceae explorada por causa da sua madeira. Esse estudo procurou caracterizar a gordura extraída de sua semente, uma parte renovável, abundante e pouco explorada da planta, cuja exploração, cuja exploração pode conciliar a preservação ambiental, o desenvolvimento regional sustentável para melhoria de vida das populações locais. Sementes coletadas e extraídas por prensagem mecânica na Comunidade do Roque localizada na Reserva extrativista do Juruá resulta numa gordura de coloração amarelada escura. Os índices físico-químicos dessa gordura foram obtidos por métodos oficiais e apresentaram alto índice de acidez e uma alta quantidade de material insaponificável. Foram realizados diferentes testes para separação dos insaponificáveis e a neutralização dessa gordura em laboratório. A gordura foi submetida a uma extração do m. insaponificável por um processo de partição líquido-líquido por 4 horas a 80 ºC, seguido de neutralização com solução alcalina. Após a otimização desse processo o m. insaponificável foi extraído em maior escala com diferentes proporções de álcoois (metanol, etanol e etanol absoluto] tendo como melhor resultado a extração com metanol 1:2 gordura /metanol). Essa fração de insaponificável extraída com metanol foi submetida a um isolamento fitoquímico por diferentes técnica cromatográficas. Foram isoladas seis substância, que foram caracterizadas por Ressonância Magnética Nuclear utilizando técnica mono-(RMN 1H e 13C) e bidimensionais (COSY, HSQC e HMBC). Foram identificados quatro neolignanas: o meso-dihidroguaiarético, a hidroxigalbolina, f 23/mpmi e o f12/14/18 e duas lactonas do tipo jurenolido C. os ensaios de atividades antioxidantes qualitativos indicaram que todas as substâncias isoladas apresentam capacidade de seqüestro de radicais livres. Após a filtragem da gordura filtrada, com índice de acidez mais elevado, foi submetido a uma transesterificação por catálise ácida homogênea com diferentes proporções de catalisador, pela via metílica. O rendimento alcançado numa única etapa foi de 58,6 % nas seguintes condições (gordura/ metanol 1:6, HCl 1 M, e temperatura 90 oC em 24 horas), esse resultado foi abaixo do esperado para catálise ácida que é acima de 90%, devido a presença de material insaponificável na gordura. A gordura que também foi neutralizada e submetida a transesterificação pela via metílica e etílica em diferentes relações molares por catálise básica homogênea (KOH, NaOH e EtONa), em diferentes proporções. O melhor resultado observado com maiores rendimentos, densidade e conversão em CCD foi de 90, 01 % nas seguintes condições (gordura/ metanol 1:9; KOH 2% e temperatura de 50 oC em 2 horas); para catálise xvi básica foi obtido 81,68 (gordura/etanol absoluto 1:12; KOH 4% e temperatura de 80 oC em 2 horas), 86,81 (gordura/etanol absoluto 1:6, NaOH 2% e temperatura de 60 ºC em 2 horas) e 82,81 (gordura/etanol absoluto 1:6, EtONa 2% e temperatura de 80 ºC em 2 horas). Tendo como melhor resulta a transesterificação com o catalisador básico NaOH. A gordura bruta e a gordura branca obtida do m.insaponificável com alto índice de acidez foi submetida a uma esterificação com catalisadores heterogêneos (FeCl3 e Fe2(SO4)3), seguidos de transesterificação em catálise básica, para obtenção de biodiesel. Foi obtido como melhor resultado 90,74 % nas seguintes condições (esterificação Fe2(SO4)3 2%; gordura/etanol 1:3 e temperatura de 90 oC em 4 horas e na transesterificação KOH 2%, gordura/etanol 1:12 e temperatura de 80 ºC em 2 horas), já ma hidrólise foi verificado melhor rendimento de 96,53 % na condições de (NaOH 4 %, gordura/ etanol absoluto 1:3 e temperatura de 90 ºC em 1 hora e na esterificação gordura/etanol absoluto 1:3; Fe2(SO4)3 2% a 90 ºC em 2 horas). A otimização do processo de preparação de biodiesel, a partir da gordura de ucuúba propiciará uma nova fontes de energia para as comunidades isoladas do interior do Estado do Amazonas.

Neolignans, dehydrodimers of phenylpropenes, are natural products that exhibit different biological activities. 8,5’-Neolignans containing a trans- dihydrobenzofuran skeleton are the most abundant neolignans in nature. The published syntheses of trans-dihydrobenzofurans are multistep procedures that are time consuming and provide the product in low yield. Furthermore, all dimerisation reactions either in the presence of enzymes or mediated by metal salts are yielding dimers consisting of two units of the same phenylpropene compound, narrowing substantially the substitution pattern. <br><br> Two different general synthetic approaches were examined. The first strategy was the enantioselective deprotonation at the α-carbon of the ο-alkyl phenols in the presence of a chiral diamine and sBuLi. Synthesis of several new phosphorous-based directed ortho-metalation groups was studied. The examined compounds having these new groups decomposed even under very mild reaction conditions and are not suitable for the application in the synthesis. The second strategy was to examine one [3+2] cycloaddition reaction, transition metal catalysed Heck oxyarylation reaction, in the synthetic approach to compounds having trans-dihydrobenzofuran skeleton. Palladium catalysed Heck oxyarylation reaction with halogenophenols or ortho-diazonium phenols as the starting material allowed the trans-dihydrobenzofuran compounds as the major products in acceptable yield and in one step. The products were formed under ligand free condition, as well as in the presence of some strong coordinating ligands (Ph3P). The experiments with several chiral ligands, showed that the obtained trans-dihydrobenzofurans were racemic mixtures. This result suggests formation of an achiral intermediate along the reaction pathway, which causes the lack of stereoselectivity in the products. Initially formed trans-dihydrobenzofuran compounds are the key precursors of many naturally occurring neolignans, and can be easily converted to 8,5’-neolignan derivatives. / 8,5’-Neolignane sind Naturstoffe die verschiedene biologische Aktivitäten ausüben. 8,5’-Neolignane mit Dihydrobenzofuran-Kernstruktur haben antioxidative Wirkung und sind als ACAT- und PAF-Inhibitoren bekannt. Zwar gibt es einige stereoselektive Synthesen von 8,5’-Neolignanen, diese sind aber kompliziert und/oder lassen nur ein eingeschränktes Substitutionsmuster zu. In der vorliegenden Dissertation wurden zwei neue Synthesewege, nämlich die Palladium-katalysierte Cycloaddition von o-Halogenphenolen und Phenylpropenen, und die α-Alkylierung, präsentiert. Diese Synthesewege führen diastereoselektiv, in ein bis drei Schritten, zu trans-Dihydrobenzofuranen, den gewünschten, potentiell bioaktiven Zielverbindungen. Ferner wurde gezeigt, dass sich ausdiesen Verbindungen verschiedene 8,5’-Neolignane schnell und einfach herstellen lassen.

Made available in DSpace on 2015-05-14T12:59:30Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 7893490 bytes, checksum: 3c73ba4d8f0de057a853ff439b7eee20 (MD5) Previous issue date: 2012-02-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The genus Krameria is the only member of Krameriaceae family, comprising 18 herbaceous or shrub species. Among these, there is Krameria tomentosa A. St.-Hil., popularly known ratanha de Nova Granada , carrapicho de cavalo or ratanha de salvanille . In this work, the isolation and structural elucidation of neolignans from the roots of K. tomentosa is described. The dried and pulverized plant material was subjected to extraction, partition and chromatography processes for isolation of chemical constituents. The chemical structures are determined by spectroscopic methods such as Infrared, 1H and 13C Nuclear Magnetic Resonance, Mass Spectrometry and comparison with literature. The hexane and dichloromethane extracts yielded five neolignans: eupomatenoid 6 and 2-(2 ,4 -dihydroxyphenyl-5-(E)-propenylbenzofuran, described for the first time in the especies, dihydrocarinatidin, described for the first time in the family, 1,1 -(E)-propenyl-4-methoxy-3,4 -oxyneolignan and 5-acid-2-(2 -hydroxy-4 ,6 -dimethoxyphenyl)-benzofuranic, described for the first time in the literature, and trivially named ottomentosa e sobralin, respectively. Thus, the obtained results contributed with chemotaxonomic knowledge of Krameriaceae family, in particular the species Krameria tomentosa. / O gênero Krameria é o único membro da família Krameriaceae, sendo composto por 18 espécies herbáceas ou arbustivas. Dentre estas, encontra-se Krameria tomentosa A. St.-Hil., conhecida popularmente como ratanha de Nova Granada , carrapicho de cavalo ou ratanha de salvanille . Neste trabalho descrevemos o isolamento e elucidação estrutural de neolignanas isoladas das raízes de K. tomentosa. O material vegetal, após secagem e pulverização, foi submetido a processos de extração, partição e cromatografia para isolamento dos constituintes químicos. A estrutura química dos mesmos foi determinada pelos métodos espectroscópicos de Infravermelho, Massas e Ressonância Magnética Nuclear de 1H e 13C uni e bidimensionais bem como por comparações com modelos da literatura. Das fases hexânica e diclorometano obtiveram-se cinco neolignanas: eupomatenoide 6 e 2-(2 ,4 -diidroxifenil-5-(E)-propenilbenzofurano, relatadas pela primeira vez na espécie, diidrocarinatidina, relatada pela primeira vez na família,1,1 -(E)-propenil-4-metoxi-3,4 -oxineolignana e 5-ácido-2-(2 -hidroxi-4 ,6 -dimetoxifenil)-benzofurânico, relatadas pela primeira vez na literatura e nomeadas trivialmente de ottomentosa e sobralina, respectivamente. Desta forma, os resultados obtidos contribuíram para a ampliação do conhecimento quimiotaxonômico da família Krameriaceae, em especial da espécie K. tomentosa.

Orientador: Prof. Dr. João Henrique Ghilardi Lago / Tese (doutorado) - Universidade Federal do ABC. Programa de Pós-Graduação em Ciência e Tecnologia/Química, 2016. / Diversas linhas de pesquisa em fitoquimica estao associadas a avaliacao de atividades biologicas visando o isolamento e caracterizacao de metabolitos ativos. Nesse contexto, foi observado que o oleo essencial, bem como os extratos das folhas de Nectandra leucantha (Lauraceae), ainda desconhecida do ponto de vista quimico, mostraram potencial antiparasitario, especialmente antileishmania e antitripanosoma. Sendo assim, o oleo essencial foi analisado por CG/FID e CG/EM permitindo a identificacao de 33 componentes, sendo o biciclogermacreno o majoritario (21,3 %). Os extratos hexanico e metanolico foram submetidos a fracionamento cromatografico, biomonitorado, frente a duas tecnicas cromatograficas diferentes (coluna aberta e em contracorrente), permitindo o isolamento de cinco neolignanas dos extratos: uma do tipo 3-3¡¦, desidrodieugenol (I) e quatro do tipo 3-O-4¡¦, desidrodieugenol B (II), 4,5-dimetoxi-3-[5'-metoxi-1'-(8'-propenil)4¡¦-fenoxi]-1-(8-propenil)benzeno (III), (S)-4-hidroxi,5-metoxi -1- [5'-metoxi-1'-(8'-propenil) 4¡¦-fenoxi]-1-(7-hidroxi-8-propenil) benzeno (IV) e (R)-4,5-dimetoxi-1-[5'-metoxi-1'-(8'-propenil)4¡¦fenoxi]-1-(7-hidroxi-8-propenil) benzeno (V), sendo III, IV e V ineditas. Alem disso, foi preparado o composto I-a, desidrodieugenol permetilado. As estruturas de todas as substancias descritas foram definidas atraves de metodos espectroscopicos e espectrometricos tais como, EM, RMN, UV, IV e DC. As substancias I-V e I-a, como os precursores, eugenol e metileugenol foram submetidos a avaliacao de suas atividades frente as formas tripomastigotas e amastigotas de Trypanosoma cruzi, promastigotas e amastigotas de Leishmania (L.) infantum e L (L.) donovani. Frente ao parasita T. cruzi, as ica do parasita, ergosterol. Desta maneira as substancias ativas encontradas neste estudo mostraram ser excelentes candidatos a desenvolvimento de farmacos visando a terapia da leishmaniose e doenca de Chagas, ja que se mostraram mais ativas e mais seletivas que os farmacos utilizados atualmente. / Several phytochemical researches are associated with evaluation of biological activities, aiming the isolation and characterization of active metabolites. In this context, it was observed that the essential oil and extracts from leaves of Nectandra leucantha (Lauraceae), specie unknown in the chemical point of view, displayed antiparasitical potential, specially antitrypanosomal and antileishmanial. Thus, essential oil was analysed by GC/FID and GC/MS allowing the identification of 33 compounds, in which bicyclogermacrene was present in higher amount (21.3%). The hexanic and methanolic extracts were subjected to a bioassay-guided chromatographic fractionation, using two different tecniques (open column and countercurrent chromatography), which afforded the isolation of five neolignans from extracts: one 3-3¡¦ neolignan type, dehydrodieugenol (I) and four 3-O-4¡¦ neolignan type, dehydrodieugenol B (II) and 4,5-dimethoxy-3-[5'-methoxy-1'-(8'-propenyl) 4¡¦-phenoxy]-1-(8-propenyl) benzene (III), (S)-4-hydroxy-5-methoxy-3-[5'-methoxy-1'-(8'-propenil) 4¡¦-phenoxy]-1-(7-hydroxy-8-propenyl) benzene (IV) and (R)-4,5-dimethoxy-3-[5'-methoxy-1'-(8'-propenyl)4¡¦-phenoxy]-1-(7-hydroxy-8-propenyl) benzene (V), which III, IV and V are described for the first time. Furthermore, the compound I-a, permethylated dehydrodieugenol was prepared. The structures of all described compounds were elucidated through spectroscopic and spectrometric methods, such as, MS, NMR, UV, IR and CD. Compounds I-V, I-a and precursors, eugenol and methyleugenol were subjected to evaluation of biological activities against trypomastigotes and amastigotes of T. cruzi and promastigotes and amastigotes of L. infantum and L. donovani. In respect of T. cruzi activities, compounally the cell death mechanism against T. cruzi parasites were evaluated for compounds I and I-a, suggesting direct action at parasites, probably related to interaction with the responsible compound of parsite cell membrance maintenance, ergosterol. Thus, the active compounds found in this study shown to be excellent candidates for drug development in the threatment of leishmaniasis and Chagas disease, as they were more active and more selective than drugs currently used.

Este trabalho descreve os isolamentos e as determinações estruturais dos metabólitos secundários das diferentes partes dos frutos (pericarpos, arilos, tegumentos e amêndoas) de Virola elongata. 0 material foi coletado em Humaitá (AM) e no Km 96 da Rodovia Santarém-Cuiabá (PA). Os constituíntes químicos foram isolados por cromatografias de adsorção e tiveram suas estruturas identificadas ou determinadas por técnicas espectrométricas usuais (IV, UV, RMN e EM). As configurações absolutas dos metabólitos foram deduzidas a partir de medidas espectropolarimétricas, ou auxiliadas pela obtenção de derivados mais informativos. As substâncias foram agrupadas nas seguintes subclasses: lignanas furofurânicas [(+)-sesamina (LF-1), (+)-epifargesina (LF-2), (+)-eudesmina (LF-3), (+)-fargesina (LF-4), (+)-filigenina (LF-5) e (+)-epieudesmina (LF-6)]; lignanas tetraidrofurânicas [(+)-magnostelina-A (LT-1), (+)-magnostelina-C (LT-2), (±)-4\'-metil-5\'-metoxi-lariciresinol (LT-3), (±)-4,4\'-dimetil-5\'- metoxi-lariciresinol (LT-4) e (±)-4-4\'-dimetil-5\'-hidroxi-5-metoxi-lariciresinol (LT-5)]; Lignana diarilbutanólica [(-)-4,4\'-dimetil-5-metoxi-secolariciresinol (LD-1)]; e lignanas dibenzilbutirolactâmicas [(-)-hinokinina (DB-1), (-)-kusunokinina (DB-2), (-)-dimetilmatairesinol (DB-3), (-)-metiltujaplicatina (DB-4), (-)-dimetil-5-hidroximatairesinol (DB-5) e (-)-dimetil-5-metoxi-matairesinol (DB-6)]; neolignanas diarilbutânicas [ND-1, ND-2 e ND-3], neolignana ariltetralínica: galbulina (NA-1) e neolignanas ariltetralônicas [(-) e (+)-oxoisogalcatina (NA-2), (+)-hidroxi-isogalcatina (NA-3), diidroxi-oxoisogalcatinas epiméricas inéditas (NA-4 e NA-5), NA-6, NA-7, (+)-otobanona (NA-8), hidroxi-otobanonas epiméricas (NA-9 e NA-10)]; neolignanas secoariltetralínicas (ND-5 e seu acetato ND-6]; uma neolignana dimérica [NA-11] e ainda diversos policetídeos acilresorcinólicos e acifloroglucinôlicos [AR-1 a AR-8]. 0 padrão 3,4-dioxigenado nos anéis aromáticos é predominante na maioria dos lignóides isolados. 0 padrão 3,4,5-trioxigenado observado nos anéis aromáticos de lignanas dibenzilbutirolactônicas (DB-4 e DB-5), diarilbutanólica (LD-1) e tetraidrofurânicas (LT-3, LT-4 e LT-5) e, o padrão 2,4,5-trioxigenado observado para neolionanas ariltetralônicas (NA-6, NA-7), conferem para algumas o caráter inédito. A maior variação no padrão de substituição de esqueletos foi observada para neolignanas ariltetralônicas, o que motivou a elaboração de experimentos especíificos em RMN- 1H (ENO e uso de reagente de deslocamento) associados a análise dos dados de RMN- 13C para proposições de constituições e de configurações relativas. Foi constatada a presença das neolionanas NA-2, NA-9 e NA-10 nos extratos dos tegumentos e de seus enantiômeros nos extratos das amêndoas de V. elongata (PA). Algumas classes de substâncias isoladas foram correlacionadas biossinteticamente a partir de suas configurações absolutas. A quantificação aproximada das substâncias identificadas foi efetuada, através das quantidades isoladas e análises de espectros de RMN-1H de frações impuras. Nos pericarpos e arilos foi constatada a presença exclusiva e alternada de lignanas furofurâanicas e lignanas dibenzilbutirolactônicas entre os frutos de diferentes localidades. Essas lignanas, também presentes nos tegumentos, ocorrem em maior teor com maior diversidade de substituição nos anéis aromáticos, mas são completamente ausentes nos extratos das amêndoas, onde o perfil é baseado na presença de neolignanas ariltetralônicas e policetídeos. Os policetídeos com anéis aromáticos di- e triidroxilados foram isolados, principalmente, dos tegumentos e amêndoas. A análise do extrato de uma das amêndoas foi baseada na análise conjunta do espectro de RMN-1H, dos cromatogramas em camada delgada e dos dados obtidos por cromatografia gasosa acoplada a espectrometria de massas. A metodologia foi tentativamente aplicada á análise das diversas partes dos frutos de V. sebifera coletada em Roraima. Os dados obtidos sobre as estruturas e distribuição dos metabólitos são confrontados com os descritos na literatura para espécies taxonomicamente afins. / This work describes isolations and structural determinations of secondary metabolites in parts of fruits (pericarps, arils, teguments and kernels) from Virola elongata. Material was collected in Humaita (AM) and Km 96 of Santarém-Cuiabá Road (PA). The chemical constituents were isolated by chromatographic processes and their structures identified or elucidated by usual spectrometric techniques (IR, UV, NMR, and MS). Absolute configuration were deduced through spectropolarimetric measures, or based on data from derivatives. The compounds were classified in the following classes: furofuran lignans [(+)-sesamin (LF-1), (+)-epifargesin (LF-2), (+)-eudesmin (LF-3), (+)- fargesin (LF-4), (+)-phylligenin (LF-5) and (+)-epieudesmin (LF-6)]; tetrahydrofuran lignans [(+)-magnostelin-A (LT-1), (+)-magnostelin-C (LT-2), (±)-5\'-methox y -4\'-methyl-lariciresinol (LT-3), (±)-5\'-methoxy-4,4\'-dimethyl-lariciresinol (LT-4) and (±)-5\'-hydroxy-5-methoxy-4,4\'-dimethvl-lariciresinol (LT-5)]; diarylbutanol lignan [(-)-4,4\'-dimethvl-5-methoxy-secolariciresinol (LD-1)]; and dibenzylbutyrolactone lignans [(-)-hinokinin (DB-1), (-)-kusunokinin (DB-2), (-)-dimethylmatairesinol (DB-3), (-)-methylthujaplicatin (DB-4)]; diarylbutane neolignans (ND-1, ND-2 and ND-3); aryltetralin neolignans [galbulin (NA-1) and aryltetralone neolignans [(-)- and (+)-oxoisogalcatin (NA-2), (+)-hydroxyisogalcatin (NA-3), unpublished epimeric dihydroxy-isogalcatins (NA-4 and NA-5), (+)-otobanone (NA-8), epimeric hydroxy-otobanones (NA-9 and NA-10)]; secoaryltetralin neolignans [ND-5 and its acetate (NA-6).1; dimeric neolignan (NA-11) and several acylresorcinol and acylphloroglucinol polyketides (AR-1 to AR-8). The 3,4-dioxygenated pattern was observed in aromatic rings of the majority isolated lignans. The 3,4,5-trioxygenated pattern observed in dibenz y lbutyrolactone lignans (DB-4 e DB-5), diarylbutanol (LD-1), and tetrahydrofuran lignans (LT-3, LT-4, LT-5), and the 2,4,5-pattern observed in aryltetralone neolignans, confer to some of them the unusual character. The main variation in the substitution pattern was observed in aryltetralone neolignans, which needed more detailed study involving 1H-NMR experiments (NOE and LIS reagent) and refined analysis of 13C-NMR data. It was observed the presence of NA-2, NA-9 and NA-10 neolignans in teguments and its enantiomers in kernels of fruits from Virola elongata (PA). The biosynthetic relationships among several classes of lignoids are discussed under their absolute configurations. The near concentration of identified compounds was obtained from isolated quantities and analysis of 1H-NMR spectra of mixtures. In pericarps and arils was determined the exclusive and alternated presence of furofuran and dibenzylbutyrolactone lignans between fruits from different localities. These last two subclasses, also present in teguments, occur in higher concentrations and substitution diversifications in aromatic rings, but are completely absent in kernels whose profile is based on the presence of aryltetralone lignans. The poliketide with di- and trihydroxylated aromatic rings were isolated mainly from teguments and kernels. The analysis from kernels extract was performed by combined analysis involving 1H-NMR spectra, thin layer chromatography, and gas chromatography coupled to mass spectrometry. This methodology was tested to analyse the parts of fruits from Virola sebifera collected in Roraima. The obtained informations about structures of metabolites and their distributions in fruits was compared with those data described for taxonomically closed species.

Woody plants are the most abundant renewable resources on the earth. From the paper we consume to the house we live in, our daily lives rely heavily on woody plants. Over the past decades, enormous efforts have been expended to improve the utilization of fiber and wood. For example, much research has been conducted to develop environmentally benign, and economically feasible techniques for pulp and papermaking. The economical conversion of wood to useful sugars and alcohol has also been the subject of intensive research. Investigations aimed at the genetic manipulation of wood growth to better meet our needs are also underway. Nonetheless, harsh pulping and bleaching conditions are still required in the pulp and paper industry, and the bioconversion of polysaccharides in biomass to alcohol is still too expensive. An argument could be put forth that a major reason for this is the lack of basic knowledge concerning the structural and biochemical characteristics of the plant cell wall. The three major polymeric components of plant cell walls, cellulose, hemicellulose and lignin, are intimately associated with one another. Cellulose is associated with hemicellulose via non-covalent linkages, whereas lignin is theorized to be associated with cellulose and hemicellulose via both covalent and non-covalent linkages. The nature of associations between wood polymers is still poorly understood. However, it is these intimate associations that make delignification difficult, and make the bioconversion of polysaccharides to alcohol inefficient. It is also believed that the linkages between lignin and polysaccharides are responsible for the reduced digestibility of grasses by ruminants. Besides cellulose, hemicellulose and lignin, there are many secondary metabolites such as lignans, neolignans, tannins and terpenoids. The structures of lignans and neolignans are analogous to the interunits of lignin. Lignin is considered an optically inactive polymer, whereas lignans and neolignans are optically active small molecules. Although it has been proposed that the biosynthesis of lignin, lignans and neolignans are via the same oxidative coupling mechanism, it is still unclear that how the plant cell wall differentiates the formation of lignans, neolignans and lignin. How and why plant cell wall generates so many lignans and neolignans having broad structural variation is also unknown. As a matter of fact, it is still uncertain which enzymes are actually involved in the biosynthesis of lignin. A better understanding of biosynthetic pathways of lignin, lignans and neolignans is a prerequisite for the genetic manipulation of plant growth. Investigations described in this dissertation were an effort to better understand the fundamental aspects of covalent linkages between lignin and hemicellulose in wood. Enantiomeric synthesis of neolignans provides a tool for investigating the optically active nature of neolignans, and may be helpful to study the biosynthetic pathways of neolignans. Chapter | describes chemical structures of wood components and the biosynthesis of lignin, lignans and neolignans. The mechanisms of lignin-carbohydrate bond formation are also discussed, and a concise review of lignin-carbohydrate linkages proposed in the literature concludes Chapter 1. Chapter 2 presents the methods used in investigating covalent linkages in wood, which include methods of isolating lignin-carbohydrate complexes, chemical cleavage methods, DDQ oxidation and model compound/NMR methods. The synthesis of plant cell wall model compounds and neolignans are reviewed in Chapter 3. The experimental work performed for the completion of this thesis is described in Chapters 4-8. A method which provides β-𝘖-4 lignin model dimers with complete threo stereospecificity is described in Chapter 4. This method is complementary to the current method for the preparation of erythro lignin model dimers. Chapter 5 presents a practical synthesis of methyl 4-𝘖-methy] α-D-glucopyranosiduronic acid. Methyl 4-𝘖-methyl-α-D-glucopyranosiduronic acid was prepared from methyl α-D-glucopyranoside in 4 steps (74% overall yield). Previous preparations of this compound were much lengthier, and had very low overall yields. Chapter 6 deals with the synthesis and rearrangement reactions of ester-linked lignin-carbohydrate model compounds. A series of ester-linked lignin-carbohydrate model compounds were synthesized, and migration of the uronosy] group between the primary (γ) and benzyl (α) position of lignin side chain is discussed. Several approaches to synthetic neolignans are described in Chapter 7. Chapter 8 presents a novel approach for the preparation of chiral aryl alkylethers. The successful application of this novel approach to synthesis of several optically active 8-𝘖-4 neolignans and a 1,4- benzodioxane neolignan is described, as is the introduction of an alkyl] aryl ether bond in carbohydrate molecules. Some of the material of this dissertation has been reported in the following papers: 1. Li, K. and Helm, R. F. Approaches to Synthetic Neolignans. J. Chem. Soc. Perkin Trans 1. Accepted. 6. Li, K. and Helm, R. F. Use of Carbohydrates as Building Blocks to Synthesize Neolignans. 211th ACS National ACS Meeting, New Orleans, March 24-28, 1996. CELL-079. 2. Li, K. and Helm, R. F. A Practical Synthesis of Methyl 4-𝘖-Methylα-D-Glucopyranosiduronic Acid. Carbohydr. Res. 273(1995), 249-253. 3. Li, K. and Helm, R. F. Synthesis and Rearrangement Reactions of Ester-Linked Lignin-Carbohydrate Model Compounds. J. Agric. Food Chem. 48(1995), 2098-2103. 4. Helm, R. F. and Li, K. Complete threo Stereospecificity for the Preparation of β-𝘖-4 Lignin Model Dimers. Holzforschung. 49(1995), 533-536. 5. Helm, R. F. and Li, K. Synthesis and Rearrangement Reactions of Lignin-uronic Acid Model Compounds Related to Hardwood Cell Wall Structure. The 8th International Symposium on Wood and Pulping Chemistry. Helsinki, Finland, June 1995, vol. 1, pp107-114. 7. Li, K. and Helm, R. F. Approaches to Synthetic Neolignans, 34th National Organic Symposium, Williamsburg, VA. June 11-15, 1995. Poster 281. / Ph. D.

A espécie vegetal Piper solmsianum (Piperaceae) é um arbusto que ocorre tanto na Mata Atlântica do Brasil quanto na Amazônia. O estudo fitoquímico aqui apresentado descreve o acúmulo dos fenilpropanóides isoelemicina, elemicina, apiol, dilapiol, mirisiticina e lignanas tetraidrofurânicas na planta adulta. Contudo, suas plântulas cultivadas e micropropagadas, com idade inferior a 9 meses, acumulam apenas fenilpropanóides. Entre as lignanas tetraidrofurânicas, a grandisina é o principal produto natural e possui potente atividade contra formas tripomastigotas de Trypanossoma cruzii, o parasita causador da Doença de Chagas. O aminoácido fenilalanina radioisotopicamente marcado é convertido nas lignanas tetraidrofurânicas. A atividade específica da enzima fenilalanina amônialiase, que converte a fenilalanina em ácido cinâmico, é dez vezes maior em plantas adultas que em plântulas. A etapa de acoplamento oxidativo que leva à formação das lignanas tetraidrofurânicas em P. solmsianum foi investigada através do E-5-metóxiisoeugenol radioisotopicamente marcado preparado por meio de uma reação de Wittig. Observou-se um acoplamento estereosseletivo e enantioespecífico formando a (-)-di-O-4,4\'-desmetilgrandisina, o precursor direto da (-)-grandisina, através do uso de preparações enzimáticas. A enzima capaz de converter o fenilpropanóide em dímero faz parte do citocromo P-450 encontrado nos microssomos celulares e é dependente de H2O2 e NADPH. Estes dados corroboram a hipótese de que os dímeros encontrados em P. solmsianum podem ser classificados como neolignanas, uma vez que são formados pelo acoplamento oxidativo de um fenilpropanóide não oxigenado na posição 9. / Piper solmsianum (Piperaceae) is a shrubb tree which occurs in both Atlantic and Rain Forests from Brazil. The phytochemical study of this species showed the accumulation of the phenylpropanoids isoelemicin, elemicin, apiol, dillapiol and myristicin and also tetrahydrofuran lignans in the adult plant. However, its cultivated and germinated seedlings of ages under 9 months accumulate phenylpropanoids only. The radioisotopically labelled aminnoacid phenylalanine is converted into tetrahydrofuran lignans. Specific activity of this enzyme, which converts phenylalanine into cinnamic acid, is ten-fold higher to adult plants than to seedlings. The oxidative coupling step which leads to the formation of the tetrahydrofuran lignans in P. Solmsianum was investigated by reaction of the isotopically labeled substrate E-5-methoxy-isoeugenol, obtained by means of a Wittig reaction, with enzyme preparations. It was observed a stereoslective and enantioespecific oxidative coupling affording (-)-di-O-4,4\'-demethyl grandisin, which is the direct precursor of (-)-grandisin. The enzyme which is able to convert the phenylpropanoid into dimer is part of cytochrome P-450 system, found in cell microssomes. This enzyme is NADPH and H2O2-dependent. These data confirm the hypothesis that these dimers found in P. Solmsianum are neolignans since they are formed by the coupling of two phenylpropanoids non-oxygenated in C-9.