A new synthetic approach to the clinically useful, anti-HIV-active nucleoside, 9-(2,3-dideoxy-2-fluoro- β-D- threo-pentofuranosyl)adenine (β-FddA). Introduction of a 2′-β-fluoro substituent via inversion of a readily obtainable 2′-α-fluoro isomer

Abstract

A convenient route to the anti-HIV active compound, 9-(2,3-dideoxy-2-fluoro- β-D- threo-pentofuranosyl)adenine ( 1, β-FddA) started with the facile introduction of fluorine at C2′ from the α-side of protected 9-(β-D-arabinofuranosyl)adenine (ara-A). Inversion of the stereochemistry at C2′ was accomplished via a stable vinyl intermediate ( 6), which underwent stereoselective reduction of the double bond to give the desired 2′-F- threo isomer with the opposite β-fluoro stereochemistry.