Abstract
Two approaches to the synthesis of the title 6-substituted 2(1H)-pyridon-3-yl C-2-deoxyribonucleosides have been pursued. A protected 6-aminopyridine C-nucleoside intermediate was converted into the N-oxide followed by rearrangement and deprotection to give 6-acetylamino-2-oxo(1H)-pyridin-3-yl deoxyribonucleoside.
Due to the unusually high stability of the N-acetyl group, the full deprotection was unsuccessful. In the second approach, 6-chloro-2-pyridone was converted into phosphorodiamidate, which underwent ortho-magnesiation and iodination to give the 3-iododerivative.
It was then used in a Heck coupling with a sugar glycal and the resulting product deprotected to give 6-chloro-2-oxo(1H)-pyridin-3-yl deoxyribonucleoside, which was converted into 6-methyl-, 6-amino-, and 6-unsubstituted pyridone C-nucleosides. The final nucleosides were very unstable which limits their further use in chemical biology.