Synthesis of L-Deoxyribonucleosides from D-Ribose

The preparation of 2-deoxy-L-ribose derivatives or mirror image deoxyribonucleosides (L-deoxyribonucleo-sides) from D-ribose is reported. Starting from inexpensive D-ribose, an acyclic D-form carbohydrate precursor was synthesized to study a unique carbonyl translocation process. In this novel radical reaction, not only was the configuration of the sugar transformed from the D-form to the L-form, but also deoxygenation at the C(2) position of the sugar was successfully achieved. This is one of the most practical methods for converting a D-sugar to a 2-deoxy-L-sugar in a one-step reaction. To further identify the reaction product, radical reactions followed by treatment with 1,3-propanedithiol and then benzoylation were performed to afford a dithioacetal derivative. The stereochemistry and configuration of the 2-deoxy-L-ribose dithioacetal derivative were confirmed by its X-ray crystal structure. To further apply this methodology, a diethyl thioacetal derivative was formed, followed by selective benzoyl protection, and an NIS-initiated cyclization reaction to give the desired ethyl S-L-2-deoxyriboside, which can be used as a 2-deoxy-L-ribosyl synthon in the formal total synthesis of various L-deoxyribonucleosides, such as L-dT.