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Efficient diastereoselective synthesis of a new class of azanucleosides: 2′-homoazanucleosides

Azanucleosides, sugar-modified nucleoside analogues containing a 4′ nitrogen atom, have shown a lot of therapeutic potential, e.g. as anti-cancer and antiviral agents. We report the synthesis of a series of 2’-homoazanucleosides, in which the nucleobase is attached to the 2’-position of the pyrrolid...

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Detalles Bibliográficos
Autores principales: Bouton, Jakob, Van Hecke, Kristof, Van Calenbergh, Serge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111761/
https://www.ncbi.nlm.nih.gov/pubmed/32287431
http://dx.doi.org/10.1016/j.tet.2017.05.083
Descripción
Sumario:Azanucleosides, sugar-modified nucleoside analogues containing a 4′ nitrogen atom, have shown a lot of therapeutic potential, e.g. as anti-cancer and antiviral agents. We report the synthesis of a series of 2’-homoazanucleosides, in which the nucleobase is attached to the 2’-position of the pyrrolidine ring via a methylene linker. A suitable orthogonally protected iminosugar was synthesized by ring closing metathesis and dihydroxylation as key steps and further converted to a series of 8 nucleoside analogues through Mitsunobu reaction with suitably protected nucleobases. The 5′ position of the adenine analogue was then further derivatized with thiols to afford 2 additional compounds. The final compounds were evaluated for biological activity.