Synthesis of 4'-thionucleosides by 1,3-dipolar cycloadditions of the simplest thiocarbonyl ylide with alkenes bearing electron-withdrawing groups

Reactions of the simplest thiocarbonyl ylide with a variety of appropriate alkenes bearing electron-withdrawing substituents afforded the corresponding tetrahydrothiophenes, which could be easily elaborated into hydroxy and hydroxymethyl derivatives and then coupled with nucleobases to produce different 40-thionucleosides. Particularly, a- and b-anomers of 1-[3,4- bis(hydroxymethyl)tetrahydro-2-thienyl]-thymine, -cytosine, -uracil and -fluorouracil were prepared with dimethyl fumarate and maleate, while 1-[4-(hydroxymethyl)tetrahydro-2-thienyl]- and 1-[4-(hydroxymethyl)tetrahydro-3-thienyl]-thymine, -cytosine, -uracil and -fluorouracil were prepared with a chiral a,b-unsaturated amide. These processes, simple in the experimental conditions and large availability of the starting materials, affording moderate to good yields of 40-thionucleosides, represent an optimum alternative to those, already known, based on sugars, which often have the drawbacks of a higher number of steps and lower yields. 2007 Elsevier Ltd. All rights reserved.