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Abstract
Late-stage functionalization has therefore emerged as a desirable approach to accelerate drug discovery5,6: much as a construction crew saws through existing walls to insert new windows, chemists aspire to cut through existing chemical bonds to insert new functional groups into molecules. Feng and colleagues are part of a research group that has long been interested in making ligand molecules that mimic the CYP450-enzyme architecture, in the hope of broadening the ability of iron complexes to transform C-H bonds into C=O bonds in diverse substrates, using hydrogen peroxide as the source of oxygen9. Feng et at. hypothesized that a less-oxidizing manganese catalyst would target the C-H bonds that are most easily metabolized on drug-like molecules. [...]they thought that the oxidation reaction could be halted midway to produce a hemi-oxidized intermediate, into which a methyl group could be inserted (Fig. 1).