Control of alpha/beta Anomer Formation by a 2',5' Bridge: Toward Nucleoside Derivatives Locked in the South Conformation

0482595 - ÚOCHB 2018 RIV US eng J - Článek v odborném periodiku
Hřebabecký, Hubert - Dračínský, Martin - Procházková, Eliška - Šála, Michal - Mackman, R. - Nencka, Radim
Control of alpha/beta Anomer Formation by a 2',5' Bridge: Toward Nucleoside Derivatives Locked in the South Conformation.
Journal of Organic Chemistry. Roč. 82, č. 21 (2017), s. 11337-11347. ISSN 0022-3263. E-ISSN 1520-6904
Grant CEP: GA ČR(CZ) GA16-20054S
Institucionální podpora: RVO:61388963
Klíčová slova: borne encephalitis virus * ring closing metathesis * nucleotide analogs
Obor OECD: Organic chemistry
Impakt faktor: 4.805, rok: 2017

We describe a novel stereoselective synthesis of nucleoside derivatives with the ribose ring locked in the South conformation by a bridge between C2' and CS'. Despite the intrinsic constraints of the bicyclic structure, we demonstrate that their synthesis can be achieved by ring closing metathesis of readily accessible precursors. The obtained ribose derivatives are, however, very poor substrates for further installation of the nucleobases, and even simple nucleophiles, such as azido or cyano anions, react with unexpected stereo- or regioselectivity under standard glycosylation conditions. Here we explain this behavior by employing density functional theory (DFT) computations and devise an alternative approach resulting in isomers with the desired orientation of the nucleobase.
Trvalý link: http://hdl.handle.net/11104/0278006