Chemists are currently able to synthetically produce almost any compound, but they must typically resort to expensive, complex processes that can require dozens of individual steps. Such natural product syntheses have traditionally relied on the ubiquitous use of protecting groups, which are extra compounds chemists use to shield reactive portions of a molecule during specific stages of a synthesis scheme. The protecting groups are eventually cleaved chemically to expose the reactive portion during later chemical reactions to complete a product's synthesis. Each protecting group used adds at least two steps to a synthesis, and the groups themselves have reactivity of their own that must be controlled to prevent adverse reactions.
Protecting groups are almost always a direct result of an inability to address selectivity in synthesis, says project leader Phil Baran, a chemist with The Scripps Research Institute. It is ironic that they often add an additional layer of problems on top of the preexisting ones.
Organic chemistry textbooks have long declared that the use of protecting groups was essential in natural product synthesis. Textbooks have pointed out that avoiding protecting groups is like avoiding death and taxes, says Baran, who, along with Scripps Research Kellogg School of Science and Technology graduate students Thomas Maimone and Jeremy Richter, has now disproved the belief.
To avoid the need for protecting groups, the Baran group took an unorthodox approach. Rather than assume that reactive portions of a molecule had to be shielded during various syntheses, the researchers calculated ways to use such reactivity in an overall scheme to produce the desired final product. Baran says the reason such an approach had not been successfully developed before was likely a by-product of education. From the beginning, we were always taught that the way to solve these types of problems is to protect functionality rather than to try t
Contact: Keith McKeown
Scripps Research Institute