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

Abstract

AbstractWe report a convenient and scalable synthetic approach for the synthesis of 3′-fluoro hexitol adenosine and guanosine nucleoside analogues and corresponding phosphoramidites in good yield. 1,5-Anhydro-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% overall yield) was accomplished, which will enable the use of 3′-fluoro hexitol nucleic acids for genetic medicine development and diagnostic applications.