In this work we demonstrate that mutations in the active site of E. coli DERA result in significantly broadened donor substrate scope allowing for the synthesis of a wide range of 2-modified-5-phosphate sugars. We have used these DERA variants to develop a one-pot synthesis of 2-functionalized D-ribose and L-lyxose-5-phosphate analogues with a range of functional groups including fluoro, MOE and OBn. Finally addition of PPM and PNP results in a one pot synthesis of adenosine analogues functionalized at the 2′-position with OH, araOH, Me and F.