5'-β,γ-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase.

The first preparation of the individual β,γ-CHF-ATP stereoisomers 12a and 12b is reported. Configurationally differing solely by the orientation of the C-F fluorine, 12a and 12b have discrete (31)P (202 MHz, pH 10.9, ΔδPα 6 Hz, ΔδPβ 4 Hz) and (19)F NMR (470 MHz, pH 9.8, ΔδF 25 Hz) spectral signatures and exhibit a 6-fold difference in IC50 values for c-Src kinase, attributed to a unique interaction of the (S)-fluorine of bound 12b with R388 in the active site.