Synthesis of 6-Alkyluridine Derivatives via Bruylants Reaction
| Autor: | Ya-Ying Yang, 楊雅媖 |
|---|---|
| Rok vydání: | 2011 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 100 The focus of this thesis is the synthesis of 6-alkyuridine derivatives as po-tential inhibitors for orotidine 5’-monophosphate decarboxylase (ODCase). 6-Alkyluridines are an important class of uridine analogs that has a syn confor-mation, in contrast to the anti conformation of uridine. The conformation of uridine derivatives play an important role in the biological system, and therefore, 6-alkyluridines have become effective probes to study the interaction between the small molecules and the biological targets. In our attempt to synthesize 6-propinoyl 1.3-dimethyluracil, the reaction of 6-cyano-1,3-dimethyluracil with ethyl magnesium bromide did not afford the desired addition product but resulted in an unexpected substitution product, 6-ethyl-1,3-dimethyluracil. The substitution reaction provided an alternative and effective route for the synthesis of 6-alkyluridine derivatives. Subsequently, 6-cyano-1,3-dimethyluracil was chosen as the reaction model to investigate the substitution reaction with Grignard reagents. In addition, the ZnCl2 as a Lewis acid was added to enhance the reaction efficiency. Our studies have shown that 6-cyano-1,3-dimethyluracil can undergo the substitution with sp3 Grignard rea-gents effectively to introduce the alkyl substituents. Therefore, the methodology was applied to an appropriately protected 6-cyanouridine and, after the deprotection, a series of 6-alkyluridine derivatives were synthesized accordingly. We have developed a novel and efficient protocol for the synthesis of the 6-alkyluridine derivatives from the corresponding 6-cyanouridines. We antici-pated that this approach will be feasible for the preparation a wide variety of 6-substituted uridine. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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