Novel phosphanucleoside analogs of dideoxynucleosides

Abstract

The synthesis of modified nucleoside analogs is an attractive area of medicinal research. Here, we have developed a synthetic route leading to a new class of dideoxynucleoside analogs, the phosphanucleosides containing 1-hydroxymethylphospholane 1-oxide rings. The preparation of these compounds consisted of a multistep synthesis of phospholane scaffold using a ring-closing metathesis and stereoselective hydroboration reaction. Subsequent nucleobase construction afforded the phosphanucleosides bearing all four nucleobases. The racemic phosphanucleosides were easily resolved on reverse phase using N-acetyl-l-tryptophan as a derivatizing agent.