Tese (doutorado) - Universidade de Brasília, Instituto de Química, 2008. / Submitted by Allan Magalhães (allanout@gmail.com) on 2011-07-01T22:06:55Z
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2008_WaleriaRodovalho.pdf: 6769419 bytes, checksum: b890debd0eff31ccefdb61989c1c7194 (MD5) / A biotina (1), uma vitamina pertencente ao complexo B, tem sido um alvo sintético atrativo devido a sua atividade biológica e aplicações em diferentes áreas como imunologia, radioterapia e bioanalítica. Nessa tese comunicamos alguns resultados experimentais para uma síntese alternativa da biotina, utilizando a hidantoína (146) como material de partida. Os compostos N-benzilado e N,N-dibenzilado, 147a e 147b, bem como os derivados 147c, 147d e 147e foram obtidos pela alquilação e acilação, respectivamente, da hidantoína. Os intermediários 147a-147e foram submetidos à condensação aldólica cruzada com 6-oxo-hexanoato de metila (148), mediada por t-BuOK 1M em THF a 0 ºC. Essas reações ocorreram somente com os compostos 147c-e, que foram convertidos no isômero Z 150a. A reatividade e influência dos grupos protetores de 147a-e e de respectivos enolatos 147a`-f` foram estudados pelo método quantum de DFT, o qual se tornou uma ferramenta útil para predizer o comportamento, em condições experimentais, desses compostos na condensação aldólica. A adição 1,4 de tioglicolato de metila (166) aos compostos 150a e 150d (protegido com Boc) foram realizadas com Et3N e a base quiral cinchonina. Para o derivado 150a, a adição conjugada com ambas as bases produziu uma mistura isomérica de 151a. Resultados similares foram obtidos para 150d usando Et3N nas mesmas condições experimentais. No entanto, a reação conjugada com esse derivado, promovida pelo alcalóide cinchonina, formou provavelmente o diastereoisômero SS 151d, confirmado pelos dados espectroscópicos (RMN 1H). As tentativas de ciclização de 151a e 151d para gerar o anel tetra-hidrotiofênico da biotina (1) não forma bem sucedidas. _________________________________________________________________________________ ABSTRACT / Biotin (1), a member of the vitamin B complex group, has been an attractive synthetic target due to its biological activity and its applications in different fields such as immunology, radiotherapy and bioanalytical chemistry. In this thesis we report some experimental results for an alternative biotin synthesis, using hydantoin (146) as starting material. The N-benzylated and N,N-dibenzylated compounds, 147a and 147b, as well as the derivatives 147c, 147d and 147e were obtained by alkylation and acylation, respectively, from hydantoin. The intermediates 147a-147e were submitted to crossed aldol condensations with methyl 6-oxo-hexanoate (148), mediated by 1M of tert butoxide of potassium. These reactions occurred only with the compounds 147c-e which were converted into the Z isomer 149a. The reactivity and influence of the protective groups of 147a-e and of respective enolate ions 147a´-f´ were studied by DFT quantum method, which showed to be a useful tool for predicting the experimental behavior of such compounds undergoing an aldol condensation. The 1,4-addition of methyl thioglycolate (166) to the compounds 150a and 150d (protected with Boc) were accomplished with triethylamine and the chiral base cinchonine. For the derivative 150a, the conjugated addition with both bases produced an isomeric mixture of 151a. Similar result for 150d was obtained using triethylamine under same experimental conditions. However, the conjugated reaction with this derivative, promoted by the alkaloid cinchonine, probably formed the SS diastereomer 151d, confirmed by spectroscopic data (1H NMR). However, the cyclization step for 151a and 151d did not to lead to the desired tetrahydrothiophenic ring of biotin (1).
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unb.br:10482/8992 |
| Date | 22 February 2008 |
| Creators | Rodovalho, Waléria |
| Contributors | Resck, Inês Sabioni |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UnB, instname:Universidade de Brasília, instacron:UNB |
| Rights | info:eu-repo/semantics/openAccess |
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