Deliberately Losing Control of C-H Activation Processes in the Design of Small Molecule Fragment Arrays Targeting Peroxisomal Metabolism.
Kahn Tareque R., Hassell-Hart S., Krojer T., Bradley A., Velupillai S., Talon R., Fairhead M., Day IJ., Bala K., Felix R., Kemmitt P., Brennan P., von Delft F., Díaz Sáez L., Spencer J., Huber K.
Combined photochemical arylation, "nuisance effect" (S N Ar) reaction sequences have been employed in the design of small arrays for immediate deployment in medium throughput X-ray protein-ligand structure determination. Reactions have been deliberately let "out of control," in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono-, bis- arylations combined with S N Ar processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.