Deliberately losing control of C-H activation processes in the design of small molecule fragment arrays targeting peroxisomal metabolism

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.