New methodology for C-nucleoside synthesis: preparation of 1,2-dideoxy-1-(3-pyridyl)-D-ribofuranose

Abstract

An eleven-step synthesis of 1,2-dideoxy-1-(3-pyridyl)-D-ribofuranose (3) from 2-deoxyribopyranose (4) is described. This procedure includes methods for selective protection/deprotection and cyclisation which should be applicable to the synthesis of other 1-substituted 1,2-dideoxyriboses. The key steps were reaction of the selectively protected D-ribose (9) with 3-lithiopyridine, and subsequent ring closure of the resultant 1-(3-pyridyl)ribitols (10) using methanesulphonyl chloride. Dideoxyriboses are of interest as nucleoside analogues for incorporation into synthetic DNA duplexes for the investigation of factors affecting DNA helix stability, especially since they are likely to cause changes in base stacking interactions.