Rational Design and Synthesis of a Fluorinated Butyric Adenosine Derivative

Pantothenate synthetase (PS), the key enzyme in the biosynthesis of the pantothenate acid, is considered to be a new target for anti-tuberculosis drug development. Based on the structure of the enzyme catalyzed reaction intermediate and bioisosterism principle, 5'-O-{[(R)-4-fluoro-2-hydroxy-3,3-dimethylbutanoyl]sulfamoyl}adenosine (1) was designed with the sulfamate isoster to replace the unstable phosphate moiety. The synthesis of this compound was achieved using pantolactone and adenosine as the starting materials through 9 steps of reaction. All the compounds were characterized by H NMR, C NMR and MS techniques.