General and Modular Synthesis of Isomeric 5-Substituted Pyridin-2-yl and 6-Substituted Pyridin-3-yl C-Ribonucleosides Bearing Diverse Alkyl, Aryl, Hetaryl, Amino, Carbamoyl, and Hydroxy Groups

0364189 - ÚOCHB 2012 RIV US eng J - Článek v odborném periodiku
Štefko, Martin - Slavětínská, Lenka - Klepetářová, Blanka - Hocek, Michal
General and Modular Synthesis of Isomeric 5-Substituted Pyridin-2-yl and 6-Substituted Pyridin-3-yl C-Ribonucleosides Bearing Diverse Alkyl, Aryl, Hetaryl, Amino, Carbamoyl, and Hydroxy Groups.
Journal of Organic Chemistry. Roč. 76, č. 16 (2011), s. 6619-6635. ISSN 0022-3263. E-ISSN 1520-6904
Grant CEP: GA MŠMT LC512; GA AV ČR IAA400550902
Výzkumný záměr: CEZ:AV0Z40550506
Klíčová slova: nucleosides * palladium-catalyzed amination * C-2'-deoxyribonucleosides * cytidine * benzene
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 4.450, rok: 2011

A general modular and practical methodology for preparation of diverse 5-substituted pyridin-2-yl and 6-substituted pyridin-3-yl C-ribonucleosides was developed. Regioselective lithiation of 2,5-dibromopyridine proceeded at the position 5- or 2- depending on the solvent and the resulting bromopyridyl lithium species underwent additions to protected ribonolactone and further transformations to hemiketals that were diastereoselectively reduced to give either 5-bromopyridine-2-yl or 6-bromopyridine-3-yl silyl-protected C-ribonucleosides. These intermediates were then subjected to a series of cross-coupling reactions, aminations, aminocarbonylations and hydroxylations to give a series of protected 1beta-(5-alkyl-, 5-aryl-, 5-amino- 5-carbamoyl and 5-hydroxypyridin-2-yl)-C-ribonucleosides and beta-(6-alkyl-, 6-aryl-, 6-amino- 6-carbamoyl and 6-hydroxypyridin-3-yl)-C-ribonucleosides. Deprotection of silylated nucleosides by Et3N.3HF, TBAF or TFA gave a series of free C-nucleosides.
Trvalý link: http://hdl.handle.net/11104/0199735