A Novel Route to Pyrimidine Isodideoxynucleosides via Michael-Type Addition on Unsaturated Modified Sugars

Abstract

A short, stereocontrolled synthesis of isonucleosides is described. This approach is based on the Michael-Type addition of silylated uracil or thymine with an appropriate acceptor as pyranoside precursor. The alkylated products obtained allow carbonyl reduction, providing a straightforward way to prepare new sugar-modified nucleosides.

Notes

these compounds are, like 3, often drawn in the Haworth representation.

Among all the described procedures to oxidize compounds of type 1, this method (see, reference 15) is interesting when glycoside 6 is wanted, otherwise, way through hemiketal 2 (R = Me) gives more versatility for other nucleosides precursors.

a) Reaction conditions have not been fully optimized; b) All yields are isolated yields; c) for data see experimental description.

As known, no racemization of C-5′ occurs in this step (see ref. 19). A single diastereoisomer was formed (Eu shift reagent, det. limit ca. 95% ee); see ref. 21.