A new process for synthesis of apricitabine, 2-(R)-hydroxymethyl-4-(R)- (cytosin-1′-yl)-1,3-oxathiolane, an Anti-HIV NRTI

Abstract

Apricitabine is a novel inhibitor of the HIV virus reverse transcriptase polymerase which is currently in clinical development for the treatment of AIDS. A new process for the preparation of apricitabine is presented which requires only three steps from 2-(R)-benzoyloxymethyl-1,3-oxathiolane. The new process produces the cis-(2R,4R) isomer in greater than 99% diastereomeric excess by preferential crystallisation of the conglomerate form of the novel 2-(R)-benzoyloxymethyl-4-(R)-(N-benzoylcytosin-1-yl)-1,3-oxathiolane intermediate without requiring chromatography. Deprotection of the intermediate in 88% yield then gives chiral apricitabine, in 30% overall yield. The new method avoids a length..