First total synthesis of 2-deoxy-4′-thio-D-xyloside, a precursor for synthesis of D-2-deoxy-4′-thionucleosides

Abstract

2-Deoxy-4′-thio-D-sugars are potential thiosugar donors for glycosylation reactions with nucleobases to produce various D-deoxy-4′-thionucleosides. However, thio-inversion reactions that produce D-deoxy-4′-thio-D-sugars depend on using a starting material, L-deoxysugar, which is expensive. Herein, we report a unique synthetic methodology to produce 2-deoxy-4′-thio-D-sugars using a D-sugar as an inexpensive starting material. Following our synthetic procedures for carbonyl translocation, d-ribose was transformed to 2-deoxy-l-ribosyl dithioacetal as a key intermediate. Mesylation and triflation provide the corresponding dialkylthio acetals as key precursors. Under thio-inversion reaction with iodide reagents, D-2-deoxy-4′-thioxyloside was successfully produced for the first time.