Development of a Novel Synthetic Process for 2-Deoxy-3,5-di-O-p-toluoyl-α-l-ribofuranosyl Chloride: A Versatile Intermediate in the Synthesis of 2‘-Deoxy-l-ribonucleosides

A novel synthetic route to 2-deoxy-3,5-di-O-p-toluoyl-α-l-ribofuranosyl chloride (1) from inexpensive d-xylose (3) is described. 1 is a key intermediate in the synthesis of the antiviral agent 1-(2-deoxy-β-l-ribofuranosyl)thymine (β-l-thymidine) (2) and other 2‘-deoxy-l-ribonucleosides. This seven-step synthesis employs a key conversion of the d to the l configuration of the sugar moiety (6 to 7 in Scheme 1) using simple reagents and reaction conditions. The entire process involves only three isolation steps. The key compound (1) was produced in 11% overall yield without chromatography.