A COMPLETELY DIASTEREOSELECTIVE ELECTROPHILIC FLUORINATION OF A CHIRAL, NONCARBOHYDRATE SUGAR RING PRECURSOR - APPLICATION TO THE SYNTHESISOF SEVERAL NOVEL 2'-FLUORONUCLEOSIDES

A new and completely diastereoselective method for the introduction of fluorine into a noncarbohydrate sugar ring precursor has been develop ed. The use of N-fluorodibenzenesulfonimide (5) for the electrophilic fluorination of chiral lactone 4, which is derived from L-glutamic aci d, yields the key intermediate 6. This is transformed into an anomeric acetate 8 and is used for the synthesis of a number of novel alpha-2' -fluoronucleosides. Since glutamic acid is used as the synthetic start ing material, the L enantiomer may also be synthesized simply by using D-glutamic acid. The incorporation of fluorine into the 2' position o f the nucleoside provides several advantages including acid stability of the anomeric bond and general resistance to oxidative metabolism. F urther, fluorine is a close mimic of hydroxyl groups in size and polar ity and in its ability to act as a hydrogen bond acceptor. This may ai d in the recognition of these nucleosides by the enzymes involved in n ucleoside activation.