912840-23-4Relevant academic research and scientific papers
New modular and efficient approach to 6-substituted pyridin-2-yl C-nucleosides
Urban, Milan,Pohl, Radek,Klepetarova, Blanka,Hocek, Michal
, p. 7322 - 7328 (2006)
A novel modular, efficient, and practical methodology of preparation of 6-substituted pyridin-2-yl C-nucleosides was developed. An addition of 2-lithio-6-bromopyridine 2b to TBDMS-protected 2-deoxyribonolactone 5 gave aduct 7 as an equilibrium mixture of anomeric hemiketals 1-(6-bromopyridin-2-yl)-1- hydroxynucleosides 7a,b and its open form 7c. Reduction of the adduct 7 with Et3SiH and BF3-Et2O afforded the desired 6-bromonucleoside 8a as pure β-anomer in a total yield of 32% over two steps from 5. Intermediate 8a was then subjected to a series of palladium catalyzed cross-coupling reactions and aminations to give a series of protected 1β-(6-alkyl-, 6-aryl-, and 6-aminopyridin-2-yl)-2-deoxyribonucleosides 9. Catalytic hydrogenation of 8a gave an unsubstituted pyridine C-nucleoside, and diazotative oxodeamination of 6-aminopyridine nucleoside 9f by isopentyl nitrite in acetic acid gave 6-oxopyridine nucleoside 10i. Deprotection of silylated nucleosides 9 by Et3N-SHF gave a series of free C-nucleosides 10.
