Professor Ohyun Kwon and her research group have invented a powerful new chemical reaction that potentially could reduce the cost of drug production.
They report this major discovery May 16 in the journal Science. 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.
The 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 oxygen and iron salt, which are inexpensive, abundant and of course, 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.
(Click on image for larger version.)
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. Pictured 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.
Penny Jennings, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.
