New modular and efficient approach to 6-substituted pyridin-2-yl C-nucleosides.
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 x Et2O afforded the desired 6-bromonucleoside 8a as pure beta-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 1beta-(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.3HF gave a series of free C-nucleosides 10.
Urban
Milan
M
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ-16610, Prague 6, Czech Republic.
Pohl
Radek
R
Klepetarova
Blanka
B
Hocek
Michal
M
D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry
D006842:Hydrocarbons, Brominated; D009705:Nucleosides; D011725:Pyridines