Synthetic approaches to novel cis and trans dideoxynucleosides of the apiose family

Abstract

Stereoselective synthesis of the complete family of optically active dideoxygenated nucleosides of the apiose family have been developed. The chiral aldodiol system 7, a key intermediate in this synthesis, was prepared from the prochiral molecule 6, through the action of the lipase from Candida cylindracia. Approaches to novel enantiomeric and diastereoisomeric dideoxynucleosides containing the tetrahydrofuranethanol moiety have also been discovered. A key intermediate in this approach was the optically active trans-allyllactone 61, prepared from L-glutamic acid, and its isomerization product, the corresponding cis-allylbutyrolactone 62. The methodologies developed have generality and allow synthetic access to a wide variety of new nucleosides.