{C-1′ Radical-Based Approaches for the Synthesis of Anomeric Spironucleosides}


Chatgilialoglu C, Gimisis T, Spada GP. {C-1′ Radical-Based Approaches for the Synthesis of Anomeric Spironucleosides}. Chem. - A Eur. J. [Internet]. 1999;5:2866–2876.


Efficient methodologies based on radical cascade reactions for the preparation of anomeric spironucleosides of general structure 3 and 4 are reported. The reactions were performed on modified uridine and 2'-deoxyuridine substrates. The protected derivatives 6 and 28 afforded the anomeric spironucleosides 7 and 29, respectively, in a stereospecific manner and in moderate yields (3-50{%}). In the 2'-deoxyribo series, the efficiency increased considerably (yields higher than 70{%}) with a concomitant decrease in stereoselectivity. In fact, the protected derivatives 13 and 21 gave mixtures of the anomeric products 11/14 and 22/23, respectively. Chemical transformations of some of these spironucleosides were successfully performed. The circular dichroism spectra of the anomeric spironucleosides displayed some striking features which can be attributed to the restricted rotation of the glycosidic bond. The reaction mechanism, which has been studied in some detail, comprises of a cascade of radical reactions in which the key step is the 1,5-radical translocation from an alkoxyl or vinyl radical. conveniently situated on the base moiety in the vicinity of the anomeric position. After the translocation, the alkoxyl radical 15, generated photolytically from an in situ prepared hypoiodite. afforded spironucleosides which possess an unusual orthoamide structure at the anomeric position. Alternatively, the vinyl radical 30, generated by the reaction of vinyl bromides with tributyltin radical, undergoes a 5-endo-trig cyclization followed by a bromine atom elimination alter the 1.5-radical translocation step.