A Facile Synthesis of 3-Fluoro Hexitol Adenosine and Guanosine Phosphoramidites

We report a convenient and scalable synthetic approach forthe synthesis of 3 '-fluoro hexitol adenosine and guanosine nucleosideanalogues and corresponding phosphoramidites in good yield. 1,5-An-hydro-4,6-O-benzylidene-D-glucitol was converted into 1,5-anhydro-4,6-O-benzylidene-3-deoxy-3-fluoro-2-O-trifluoromethanesulfonyl-D-altritol in a three-step process. Glycosylation using adenosine or 2-amino-6-iodopurine yielded the corresponding nucleoside analogues in excellent yield. Based on this strategy, a highly concise and scalable synthesis of 3 '-fluoro hexitol purine nucleosides (1-2 g, 18-21% overallyield) was accomplished, which will enable the use of 3 '-fluoro hexitolnucleic acids for genetic medicine development and diagnostic applications.