Fluoromethyl, difluoromethyl, and trifluoromethyl groups
are present
in numerous pharmaceuticals and agrochemicals, where they play critical
roles in the efficacy and metabolic stability of these molecules.
Strategies for late-stage incorporation of fluorine-containing atoms
in molecules have become an important area of organic and medicinal
chemistry as well as synthetic biology. Herein, we describe the synthesis
and use ofTe-adenosyl-L-(fluoromethyl)homotellurocysteine
(FMeTeSAM), a novel and biologically relevant fluoromethylating agent.
FMeTeSAM is structurally and chemically related to the universal cellular
methyl donorS-adenosyl-L-methionine
(SAM) and supports the robust transfer of fluoromethyl groups to oxygen,
nitrogen, sulfur, and some carbon nucleophiles. FMeTeSAM is also used
to fluoromethylate precursors to oxaline and daunorubicin, two complex
natural products that exhibit antitumor properties.