Whereas monofluorinated ATP has shown moderate success on 19F NMR-based methods for an ATP utilizing enzyme (e.g., kinase) screening experiments, 2-trifluoromethyl (2-CF3) ATP can produce better signal to noise ratio on 19F NMR spectroscopy due to the three fluorines in its structure. It is expected to obtain better result on 19F NMR enzyme screening analysis with 2-CF3 ATP compared to using monofluorinated ATP. We are proposing to make 2-CF3 ATP by a multi-step synthesis. First, the hydroxyl groups on 2', 3', and 5' positions are protected by acetyl groups. Then, the carbonyl oxygen on the 4 position of guanosine is substituted with chlorine. Next, the amine group on the 2 position is substituted with iodine. The chlorine on the 4 position is substituted to ammonia and the acetyl groups on 2', 3', and 5' positions are hydrolyzed to remove the protecting groups (2-iodo adenosine). Then the iodine on the 2 position will be substituted with a trifluoro group. Finally, a triphosphate group will be added on the 5' position. In initial experiment, a small amount of 2-iodo adenosine has been synthesized by replicating literature procedures. Currently, an alternative method for forming a 2-iodo adenosine is being tried by trapping ammonia in a pressure tube in order to increase the reactivity and yield. Purityof each product from each step is confirmed by 1H and 13C NMR spectroscopy and melting point analysis.

Synthesis of 2-trifluoromethyl adenosine triphosphate from guanosine for nuclear magnetic resonance spectroscopy

246th National Meeting (2013)

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