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Síntese e funcionalização de ribonolactonas
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O presente trabalho procurou estabelecer as condições adequadas para a introdução seletiva de alcenos ligados à posição 5 da L-ribonolactona sem perda de quiralidade em nenhum dos 3 átomos de carbono quirais desta lactona obtida diretamente da “chiral pool”. A importância da ribonolactona reside na sua versatilidade como bloco de construção quiral, cuja elevada densidade funcional e configuração estereoquímica são bem definida. A L-ribonolactona, foi facilmente acessível a partir de açúcares como a L-ribose, apresentando elevada densidade funcional e centros estereogênicos definidos, características que a tornam um ponto de partida estratégico para a construção de moléculas de interesse. O foco do trabalho manteve-se na obtenção e funcionalização de derivados da L-ribonolactona através de reações de proteção seletiva de grupos hidroxilos, oxidações, olefinações, sempre com o objectivo de explorar a modificação seletiva deste núcleo permitindo o acesso a uma ampla gama de derivados, que podem atuar como blocos de construção para a síntese de estruturas complexas. A funcionalização ortogonal dos grupos hidroxilo presentes nas posições 2 e 3 da L ribonolactona, obtida pela formação de um cetal, possibilitou a modificação seletiva da posição 5. Nesta posição, foi possível introduzir a função aldeído por oxidação de Swern ou, alternativamente, um átomo de iodo, criando assim substratos adequados para reações de olefinação do tipo Wittig ou Julia. Os ensaios realizados a partir do derivado iodado 5-iodo-2,3-O-isopropilideno-L-ribonolactona demonstraram a formação bem-sucedida do ileto de fósforo, configurando-se como uma alternativa sintética viável e com potencial para futuras aplicações. Já a tentativa de olefinação de Julia, partindo do mesmo derivado iodado, não resultou na formação do produto desejado, indicando a necessidade de novos ensaios e otimização das condições reacionais para viabilizar essa rota. Por outro lado, a rota envolvendo a oxidação de Swern a partir do composto 2,3-O-isopropilideno-L-ribonolactona, seguida da utilização do intermediário aldeído na reação de Wittig formando o composto (3S,6S,6S)-2,2 dimetil-6-((E)-estiril)dihidrofuro[3,4-d][1,3]dioxol-4(3H)-ona, mostrou-se mais promissora, permitindo a identificação de ambos os isómeros cis e trans, embora ainda necessite de optimização das condições reacionais.
The present work sought to establish the appropriate conditions for the selective introduction of alkenes at the C-5 position of L-ribonolactone without loss of chirality at any of the three chiral carbon atoms of this lactone, which is directly obtained from the chiral pool. The importance of ribonolactone lies in its versatility as a chiral building block, characterized by a high functional density and a well-defined stereochemical configuration. L-Ribonolactone was readily accessible from sugars such as L-ribose, exhibiting a high degree of functionalization and well-defined stereogenic centers— features that make it a strategic starting point for the construction of molecules of interest. The focus of this work was the preparation and functionalization of L-ribonolactone derivatives through selective protection of hydroxyl groups, oxidations, and olefinations, with the overall goal of exploring the selective modification of this core structure to enable access to a wide range of derivatives that can serve as building blocks for the synthesis of complex structures. The orthogonal functionalization of the hydroxyl groups at positions 2 and 3 of L-ribonolactone, achieved through ketal formation, enabled the selective modification of position 5. At this position, it was possible to introduce an aldehyde function via Swern oxidation or, alternatively, an iodine atom, thereby creating suitable substrates for Wittig or Julia olefination reactions. The experiments carried out using the iodinated derivative 5-iodo-2,3-O-isopropylidene-L-ribonolactone demonstrated the successful formation of the phosphorus ylide, establishing it as a viable synthetic alternative with potential for future applications. However, the attempt at Julia Olefination, starting from the same iodinated derivative, did not yield the desired product, indicating the need for further experiments and optimization of the reaction conditions to make this route feasible. On the other hand, the route involving Swern oxidation of 2,3-O-isopropylidene-L-ribonolactone, followed by the use of the aldehyde intermediate in the Wittig reaction to form (3S,6S,6S)-2,2-dimethyl-6-((E) styryl)dihydrofuro[3,4-d][1,3]dioxol-4(3H)-one, proved more promising, allowing the identification of both cis and trans isomers, although it still requires optimization of the reaction conditions.
The present work sought to establish the appropriate conditions for the selective introduction of alkenes at the C-5 position of L-ribonolactone without loss of chirality at any of the three chiral carbon atoms of this lactone, which is directly obtained from the chiral pool. The importance of ribonolactone lies in its versatility as a chiral building block, characterized by a high functional density and a well-defined stereochemical configuration. L-Ribonolactone was readily accessible from sugars such as L-ribose, exhibiting a high degree of functionalization and well-defined stereogenic centers— features that make it a strategic starting point for the construction of molecules of interest. The focus of this work was the preparation and functionalization of L-ribonolactone derivatives through selective protection of hydroxyl groups, oxidations, and olefinations, with the overall goal of exploring the selective modification of this core structure to enable access to a wide range of derivatives that can serve as building blocks for the synthesis of complex structures. The orthogonal functionalization of the hydroxyl groups at positions 2 and 3 of L-ribonolactone, achieved through ketal formation, enabled the selective modification of position 5. At this position, it was possible to introduce an aldehyde function via Swern oxidation or, alternatively, an iodine atom, thereby creating suitable substrates for Wittig or Julia olefination reactions. The experiments carried out using the iodinated derivative 5-iodo-2,3-O-isopropylidene-L-ribonolactone demonstrated the successful formation of the phosphorus ylide, establishing it as a viable synthetic alternative with potential for future applications. However, the attempt at Julia Olefination, starting from the same iodinated derivative, did not yield the desired product, indicating the need for further experiments and optimization of the reaction conditions to make this route feasible. On the other hand, the route involving Swern oxidation of 2,3-O-isopropylidene-L-ribonolactone, followed by the use of the aldehyde intermediate in the Wittig reaction to form (3S,6S,6S)-2,2-dimethyl-6-((E) styryl)dihydrofuro[3,4-d][1,3]dioxol-4(3H)-one, proved more promising, allowing the identification of both cis and trans isomers, although it still requires optimization of the reaction conditions.
Descrição
Palavras-chave
Ribonolactonas L-ribose funcionalização ortogonal oxidação Swern reação de Wittig