One of the most elegant and efficient ways to build a complex organic molecule comes from nature: the production of terpenes. It begins with a few amazingly simple starting materials such as isopentenyl pyrophosphate and strings them together to form what is known as a polyolefin precursor. A cascade reaction then sets in, in which enzymes link the carbon atoms of the long molecule at the right places to form rings, thus creating a complex three-dimensional structure.
For almost 100 years, terpene biosynthesis has served as the benchmark against which synthetic organic chemists measure their skill. So did Phil Baran from the Californian Scripps Research Institute. His group has now made an unusual attempt to create compounds that are as sophisticated as enzymes. To do this, she used a tool that most professionals in the field avoid: an electric current.
Many previous approaches have focused on perfecting polycyclization—the sophisticated formation of the ring system from a given polyolefin precursor. Ultimately, this results in a tailor-made route to a specific molecule. However, Phil Baran’s team had something else in mind: they were looking for a way to modularly assemble the polyolefin precursor from simple building blocks. The small molecules would have to split off CO2 easy to link together, that’s her idea. They wanted to find general conditions for this decarboxylation, as the reaction is called in technical jargon, so that a variety of terpenes could be produced by varying the starting materials. Instead of a tailor-made route for a special natural substance, they would thus create broad access to an entire class of substances.