A synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine via a bromine rearrangement during fluorination with MOST reagent

A facile method for the synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine 6 has been developed. Fluorination of 5′-O-acetyl-3′-β-bromo-3′-deoxyadenosine 3 with MOST gave 2′-β-bromo-3′-α-fluoro-2′,3′-dideoxyadenosine 4 via a rearrangement of the 3′-β-bromine to the 2′-β position during 3′-α fluorination. The 2′-β bromine was reduced by radical reduction and then the 5′-O-acetyl group was removed to afford 3′-α-fluoro-2′,3′-dideoxyadenosine 6 in good yield. A possible mechanism for the rearrangement is discussed.

Graphical abstractA facile bromine rearranging fluorination is applied for the synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine. Figure optionsDownload full-size imageDownload as PowerPoint slide