Publication: Nuevas estrategias de glicosidación para la síntesis de oligosacáridos de interés biológico
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2017-05-12
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Universidad Complutense de Madrid
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Abstract
En este trabajo se ha evaluado la utilidad de 1,2-ortoésteres de metilo (MeOEs) como dadores de glicosilo en estrategias de glicosidación. En primer lugar, se ha llevado a cabo un estudio de su regioselectividad en reacciones de glicosidación empleando diferentes polioles como aceptores. Los resultados obtenidos se han comparado con los obtenidos previamente por 1,2-ortoésteres de pentenilo (NPOEs). Ambos dadores de glicosilo dieron resultados similares frente a diferentes tipos de aceptores, si bien los NPOEs mostraron ser algo más regioselectivos. Esta discrepancia en regioselectividad podría ser explicada en base a diferentes especies catiónicas intermedias implicadas en la activación de MeOEs y NPOEs. Por otro lado, los MeOEs presentan la ventaja del bajo coste del metanol, en comparación con el alcohol n-pentenílico presente en NPOEs. Adicionalmente, se ha estudiado la formación estereocontrolada de disacáridos 1α,1́β tras la activación con BF3·Et2O de algunos 1,2-ortoésteres de metilo. Como prueba de la versatilidad de MeOEs en procesos de glicosidación, se ha desarrollado un método eficiente y sencillo para la preparación de fluoruros de glicosilo a partir de 1,2-ortoésteres de alquilo. Esta metodología, basada en el empleo de HF-Piridina como catalizador ácido y fuente de anión fluoruro nucleófilo simultáneamente, ha probado ser un método útil que es además compatible con la presencia de diferentes grupos protectores así como de hidroxilos libres en los ortoésteres de partida. Los fluoruros de glicosilo sintetizados, han sido empleados en estrategias de glicosidación ortogonales y bi-direccionales...
In this work we have evaluated the scope of methyl 1,2-orthoesters (MeOEs) as donors in glycosylation strategies. Firstly, we carried out a study of the regiopreferences associated to MeOEs in glycosylation reactions using several monosacharide-polyols as acceptors. In general, the results obtained were in agreement with those previously observed with n-pentenyl 1,2- orthoesters (NPOEs), although NPOEs displayed a slightly higher regioselectivity in certain instances. This discrepancy in regioselectivity has been ascribed to the existence of different reactive intermediates arising from MeOEs or NPOEs. On the other hand, MeOEs have the advantage of the low cost of methanol compared to that of n-pentenyl alcohol present in NPOEs. Additionally, we have studied the observed formation of mannose 1α,1́β disaccharides in the BF3·Et2O-mediated reaction of certain MeOEs. As proof of the versatility of MeOEs in glycosylation processes, an efficient method for the preparation of glycosyl fluorides from MeOEs has been developed. This protocol is based in the use of HF-pyridine complex as a reagent that functions simultaneously as an acid catalyst and as source of nucleophilic fluoride. The method has proven to be compatible with the presence of different protecting substitunts as well as that of free hydroxyl groups in the starting MeOEs. The ensuing glycosyl fluorides have been used in orthogonal and bi-directional glycosylation strategies...
In this work we have evaluated the scope of methyl 1,2-orthoesters (MeOEs) as donors in glycosylation strategies. Firstly, we carried out a study of the regiopreferences associated to MeOEs in glycosylation reactions using several monosacharide-polyols as acceptors. In general, the results obtained were in agreement with those previously observed with n-pentenyl 1,2- orthoesters (NPOEs), although NPOEs displayed a slightly higher regioselectivity in certain instances. This discrepancy in regioselectivity has been ascribed to the existence of different reactive intermediates arising from MeOEs or NPOEs. On the other hand, MeOEs have the advantage of the low cost of methanol compared to that of n-pentenyl alcohol present in NPOEs. Additionally, we have studied the observed formation of mannose 1α,1́β disaccharides in the BF3·Et2O-mediated reaction of certain MeOEs. As proof of the versatility of MeOEs in glycosylation processes, an efficient method for the preparation of glycosyl fluorides from MeOEs has been developed. This protocol is based in the use of HF-pyridine complex as a reagent that functions simultaneously as an acid catalyst and as source of nucleophilic fluoride. The method has proven to be compatible with the presence of different protecting substitunts as well as that of free hydroxyl groups in the starting MeOEs. The ensuing glycosyl fluorides have been used in orthogonal and bi-directional glycosylation strategies...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Química Orgánica I, leída el 17-12-2015