Drug development: are you ready to go organic?
CORVALLIS, Ore.—Researchers at Oregon State University (OSU) have developed a new “organocatalyst” that is expected to make a big change in the world of new drug development. The catalyst, Hua Cat, is a result of support from the University Venture Development Fund, an initiative set into motion in 2007 by the Oregon Legislature. The venture is intended to create jobs and boost business by supporting university-based discoveries and moving them towards commercial use.
The catalyst is the result of venturing into the field of organocatalysis, the development of catalysts for drug production that do not use toxic or precious metals. Dr. Rich Carter, a professor of chemistry at OSU, is co-inventor of this new catalyst, alongside Hua Yang, a postdoctoral research associate at OSU. Carter and the other researchers had started their project while trying to synthesize a molecule known as lypopodene.
“We were kind of led down this path by the fact that none of the catalyst systems out there in the literature were able to do the transformation that we needed, and so we developed this catalyst really out of necessity to solve a specific problem, but it was only after that that we discovered it was so generally useful,” says Carter.
The Hua Cat catalyst is derived from the amino acid proline, as well as other compounds such as soaps and cleaning solvents. Catalysts work to facilitate other chemical reactions without being consumed in the process. They play an important part in drug development by transforming the compounds into chiral molecules, in a process that Carter describes as being similar to shaking hands.
“If you take your left and right hands, you can’t actually superimpose them on another and make a superimposable mirror image. That’s called chirality,” Carter explains. “The catalyst is left-handed or right-handed, and so when it interacts with the new molecule, just like shaking hands, one interaction’s are better—the right hand shaking with the right hand’s better than the right hand shaking with the left hand. And so it transfers its chirality to the new molecule.”
Current catalysts are made from a variety of different materials, Carter says, with many derived from proline like the Hua Cat catalyst. Some catalysts are made from other amino acids, others from metals like osmium, refinium and rodium and still others are derived from alkaloids.
The organocatalysts can make drug development easier, Carter says, but in other ways it simply represents “a practical advantage.”
“Some of the other catalysts use toxic metals or expensive metals and can be much more expensive to prepare,” Carter explains, adding that proline is both plentiful and renewable. “So one advantage to organocatalysts as a class is that they’re more environmentally friendly because they’re derived from organic molecules, and they often tend to be a lot less expensive because they don’t involve toxic or very precious metals.”
The increased solubility of Carter’s catalyst, which is 10 times higher than that of current catalysts, is an extremely important factor in its favor, he says. Given the human body’s high water content and the fact that most amino acids are highly polar, the polar molecules must be able to dissolve readily in water.
“In industry, polar compounds are sometimes difficult to deal with, and they really would like to have more non-polar compounds, because they’re solvents that you do the reactions in,” says Carter. “They can recover easier and do a lot of the experiments in non-polar solvents, which are advantageous to them for drug development plus savings, because you’re able to do these reactions in solvents that you can recycle and reuse, and it makes isolation of products often a lot easier.”
Carter and Yang developed the catalyst in collaboration with and with the support of Albany, Ore.-based Synthetech, a contract manufacturer of pharmaceutical products. OSU has patented the technology and is licensing use of the catalyst to private industry.
“Hua Cat is very user-friendly for drug development—simple but effective,” says Michael Standen, director of technology for Synthetech. “It’s this type of inventive, creative technology, and our close relationship with the university, that is helping us to keep jobs and production here in Oregon and the U.S.”
Research is continuing to find variants of the catalyst with other applications. While Carter admits that organocatalysis is a young science, “we believe it’s about ready to take off and provide improved methods for drug research and development.” Standen echoes the statement, adding that they believe organocatalysis is ready “to become an important part of a $350 billion drug development industry.”
“These types of catalysts can be used in the development of almost any type of drug, whether they are for treating cancer, heart disease, infectious disease or other health problems,” says Carter. “At the same time, OSU students are now gaining an edge in the new era of environmentally-friendly medicinal chemistry.”