Chemists synthesized a highly complex natural molecule through a revolutionary strategy of functionalizing normally inert carbon-hydrogen (C-H). Science published the breakthrough led by chemists at Emory University and Caltech.
The work is the most dramatic example yet of a sequence of C-H functionalization reactions selectively transforming low-cost materials into complex building blocks of organic chemistry.
Ten of the steps involved in their synthesis of cylindrocyclophane A — a natural compound with antimicrobial properties — involved C-H reactions.
“It’s by far the most complex natural product we have made using our method,” says Huw Davies, Emory professor of chemistry and co-corresponding author of the paper. “This is a game changer. We’re doing chemistry on C-H bonds that formerly would have been considered as unreactive. And we’ve shown how we can orchestrate a suite of 10 C-H functionalization steps, targeting a single C-H bond at a time in a specific sequence.”
“This work moves the field forward by showing the power of C-H functionalization,” adds Brian Stoltz, professor of chemistry at Caltech and co-corresponding author of the paper. “It will open people’s eyes to the possibilities of using these very selective and unusual transformations in a really complex setting.”
First author is Aaron Bosse, who did the work as an Emory PhD student. Bosse has since graduated and is now a medicinal chemist at Takeda Pharmaceuticals in Cambridge, Massachusetts.
