A New Process for Synthesis of Apricitabine, 2-(R)-Hydroxymethyl-4-(R)-(cytosin-1 '-yl)-1,3-oxathiolane, an Anti-HIV NRTI

作者：Marcuccio Sebastian M; Epa Ruwan; White Jonathan M; Deadman John J^*

来源：Organic Process Research & Development, 2011, 15(4): 763-773.

DOI：10.1021/op2000332

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)-benzoyloxymethy1-4-(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 lengthy salt formation/-break stage, does not require toluene sulphonic acid, and introduces no new byproduct to the manufacturing process.

• 出版日期2011-8