Issue Date: February 27, 2012
Arthur C. Cope Scholar: Timothy F. Jamison
Timothy F. Jamison’s penchant for making and mixing things can be traced back to his part-time job in high school at Swensen’s, an ice cream parlor where he made 100 or so gallons of the treat on a typical afternoon.
At age 44, Jamison is still enamored with making and mixing things, but of a different kind. Inspirational high school teachers and a formative undergraduate research experience convinced him to trade ice cream for more challenging synthetic targets. Now, as a chemistry professor at Massachusetts Institute of Technology, Jamison develops new synthetic methods and uses them to make natural products.
“Tim Jamison has made numerous substantial contributions to the array of synthetic methods available to organic chemists,” says fellow MIT organic chemist Stephen L. Buchwald.
The cornerstone of those contributions is nickel. The Jamison lab has devised nickel-catalyzed transformations for reductively coupling alkynes with aldehydes, for combining α-olefins with aldehydes, and for coupling alkynes and alkenes with epoxides.
The last reaction goes against the normal dogma that both reactants need a multiple bond for the coupling reaction to proceed with low-valent metals, Buchwald says.
To demonstrate the power of these nickel-catalyzed synthetic reactions, Jamison has used them to complete “a number of innovative and efficient total syntheses of interesting natural products,” Buchwald says.
Among them is a route to terpestacin, a molecule isolated from a fungus that has been shown to inhibit angiogenesis and interfere with HIV infection mechanisms. Jamison’s team members used their nickel chemistry to stitch together the natural product’s 15-member macrocycle and to correct the structure of its purported diastereomer.
His team later used nickel methods to diastereoselectively construct the 18-member macrocycle of amphidinolide T1, a marine natural product with antitumor properties. And they used their nickel-based strategies to build acutiphycin, a macrocycle of similar size and activity isolated from blue-green algae.
More recently, Jamison “obtained the first real solution to the 20-year-old problem of modeling the chemistry proposed by Columbia University’s Koji Nakanishi for the biosynthesis of ladder polyether natural products,” Buchwald says.
Ladder polyethers are behind the toxic algae blooms commonly known as red tides. Back in 1985, Nakanishi proposed that the algae made such ladder polyethers by way of a cascade of enzyme-catalyzed epoxide-opening reactions. Two decades later, after many other chemists had tried and failed, Jamison’s team managed to model Nakanishi’s proposed chemistry. The key was carrying out the chemistry in water at neutral pH—just as nature does.
Jamison’s team went on to demonstrate that its epoxide cascade chemistry can be used to make various natural products containing ladder polyether motifs.
A native of northern California, Jamison got his undergraduate degree in chemistry at the University of California, Berkeley. A Fulbright fellowship then took him to the Swiss Federal Institute of Technology (ETH), Zurich. He then completed his graduate degree in chemistry as well as a postdoc at Harvard University. He started his independent career in 1999 at MIT, where he has remained ever since.
- Chemical & Engineering News
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