From sugars to modified nucleosides

Abstract

Two strategies are reported for the diastereoselective synthesis of isoxazolidinyl nucleosides, as potential antiviral agents - a one-step approach based on 1,3-dipolar cycloaddition of sugar- derived nitrones with vinyl nucleobases derived from uracil and adenine, as well as a two-step methodology based on the Vorbrüggen nucleosidation of the 5-acetoxyisoxazolidines. The 1,3- dipolar cycloadditions of sugar-derived nitrones with vinyl acetate proceed with very good diastereoselectivity to give the diastereoisomeric isoxazolidines. Condensation of the major diastereomerically pure acetoxyisoxazolidines with silylated uracil, thymine, cytosine, Nacetylguanine and purines occurs with moderate to excellent stereoselectivity with the formation of the expected isoxazolidinyl nucleosides. The stereoselectivity of the addition of the silylated nucleobase is dependent on the structure of the substituent at C-3 originating from the starting chiral nitrone and on the attacking nucleobase.