Ohyun Kwon wins the prestigious 2019-2020 McCoy Award, which recognizes the greatest contribution of the year to the science of chemistry and biochemistry.
Professor Ohyun Kwon has discovered a new very general reaction, the hydrodealkenylation, a reaction that clips a propenyl group or other alkenyl group off and replaces it with an H. (A propenyl group is a common substituent in terpenoid natural products). This discovery changes the way that many organic syntheses will be planned, and as a result, will reduce the cost of chemicals and pharmaceuticals.
Each year, the Herbert Newby McCoy Award is given to the UCLA Department of Chemistry & Biochemistry faculty member, postdoctoral researcher, or student who has made the greatest contribution of the year to the science of chemistry and biochemistry. This year the award comes with an $8,000 prize. The first recipient of the award in 1965 was Nobel Laureate Professor Donald Cram.
The department will properly honor Kwon in the future at the 2020 Departmental Awards Ceremony, on a date to be determined.
“It is such pleasure to see an innovative, truly beautiful reaction being discovered in this day and age!” said nominator Professor Yves Rubin. “For those familiar with organic chemistry, I believe that this is the type of work that can be described as incredibly sophisticated, yet so simple in its concept. The type of discovery for which someone would say: ‘why didn’t I think about this?’”
Comments by reviewers of Kwon’s Science paper reporting the research reflect its importance: “It is amazing that no one has ever discovered this before,” “It represents a major discovery,” and “This is an outstanding paper that fills a significant void in the preparation of synthetic intermediates.” Renowned chemist, Stuart L. Schreiber wrote, “This is so AMAZINGLY cool! Brilliant! These are the amazing transformations, those that will have a big impact on organic synthesis!”.
Kwon has invented more than 30 reactions at UCLA. This is the first reaction she has patented. A perspective on the research was also featured in the same issue of Science.
The Science paper describes the design and implementation of a broadly applicable and procedurally simple conversion of the C(sp3)–C(sp2) bonds to C(sp3)–H linkages — a transformation the researchers call “hydrodealkenylation.”
Kwon’s new reaction has combined six steps into one, in one of the examples. The reaction will enable organic chemists around the world to reduce their costs and do reactions in much less time. It also provides chiral synthetic intermediates that were previously not available. One chemical reaction step usually increases the cost by 10-fold, Kwon said. If chemists have to go through six steps, then they would have to raise the price by a factor of one million, she added.
The chemicals used in the reaction are readily available, inexpensive natural chemical building blocks that have been used by synthetic chemists for years. The reaction uses a reactive form of oxygen, ozone, and an iron salt, which are inexpensive, abundant and importantly, non-toxic. Kwon’s new reaction can be done in a regular laboratory.
The figure below shows how the reaction can save in production costs:
Applications of hydrodealkenylative fragmentation of C(sp3)–C(sp2) bonds. (A) Expedited synthesis of complex natural product. (B) Facile generation of chiral synthetic intermediate.
Each step in a synthesis is often accompanied by the formation of carbon centers with “precisely defined stereochemical arrangement.” Asymmetric synthesis, particularly when providing a single enantiomer, remains one of the most significant challenges in chemical synthesis, Kwon said. What has been lacking, until now, is a general method for transforming readily available chiral pool–based starting materials in a predictable manner.
Kwon and her research team envisioned a “deconstructive strategy employing alkene precursors, involving the conversion of C(sp3)–C(sp2) bonds to C(sp3)–H linkages.” They describe how the use of ozone, an iron salt, and a hydrogen atom donor (benzenethiol) is an effective strategy that yields a number of hydrodealkenylated products in great yields.
Chemical companies are interested in making the products from Kwon’s hydrodealkenyaltion commercially available. UC has filed a provisional patent on the process with Kwon and her graduate student, Andrew Smaligo, as inventors.
The title of the paper is “Hydrodealkenylative C(sp3)–C(sp2) bond fragmentation.” The lead author is graduate student Andrew Smaligo, co-authors are research assistant Manisha Swain, and graduate students Jason Quintana, Mikayla Tan, and Danielle Kim. Kwon is the senior author. Photo above:
The Kwon group research team – Jason Quintana, Professor Ohyun Kwon, first author Andrew Smaligo, and Dr. Manisha Swain.
Kwon’s UCLA research focuses on the development of new reactions and reagents, as well as synthesis of complex natural products and potential pharmaceutical agents. Kwon has developed 22 patented drug candidates and 13 commercialized chemicals. In 2018, she was awarded the 2018 Boehringer Ingelheim Green Chemistry Award and a $200,000 Technology Development Award from the University of California Center for Accelerated Innovation. She also received the 2019 Novartis Chemistry Lectureship Award. To learn more about Kwon’s research, visit her group’s website. The news was featured on UCLA Newsroom on August 14, 2020.
Penny Jennings, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.
