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 sugarderived 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.

Synthesis and biological activity of potential antiviral compounds through 1,3-dipolar cycloadditions. Part 2: nitrones, nitrile oxides and imines, and other 1,3-dipoles

“…The first one deals with the synthesis of antiviral compounds from non-carbohydrate precursors 88 while the second specifically applies the chemistry of sugars towards modified nucleosides. 89 Nitrones behave differently with respect to azides 1 since their chemistry represents the main route towards isoxazolidines that are valuable heterocyclic scaffolds for the synthesis of N,O-nucleosides. The easy way by which nitrones can be prepared offers a wide variety of solutions for the construction of nucleosides and analogues through variable synthetic strategies.…”