Melodie Christensen, Senior Scientist at Merck, is the 2017 winner of The Journal of Organic Chemistry Outstanding Publication of the Year Lectureship. The Journal of Organic Chemistry and the ACS Division of Organic Chemistry sponsor this annual award, which honors the author of an outstanding article published in the previous calendar year that demonstrates creativity and impact in the field of organic chemistry.
Melodie was selected for this honor in large part because of the outstanding science in her paper Enantioselective Synthesis of α-Methyl-β-cyclopropyldihydrocinnamates, says The Journal of Organic Chemistry Editor-in-Chief Scott J. Miller. “Melodie’s paper was universally esteemed by our selection committee as a tour de force of stereoselective synthesis, with state-of-the-art approaches, applied to a very difficult molecular scaffold.
“Melodie’s selection is exciting for the science her paper represents, but it is also perhaps worth noting that this will be the first time the JOC Lectureship Award is being bestowed upon a colleague from industry (as opposed to academia),” Scott said.
The Journal of Organic Chemistry Outstanding Publication of the Year Lectureship Session at the 2017 ACS Fall National Meeting
As winner of The Journal of Organic Chemistry Outstanding Publication of the Year Lectureship for 2017, Melodie will present at an ACS Division of Organic Chemistry session in her honor at the 2017 ACS Fall National Meeting in Washington, D.C. The session will also celebrate Xile Hu, winner of Organic Letters Outstanding Publication of the Year Lectureship for 2017. The Journal of Organic Chemistry, Organic Letters, and the ACS Division of Organic Chemistry encourage you to attend the session on Sunday, August 20, 1 p.m. to 5 p.m.
An Interview with Melodie Christensen
I connected with Melodie recently to learn more about her research and her career in organic chemistry. These are the highlights off our conversation.
How did you become interested in organic chemistry and how did your career progress to working in drug discovery and development?
As a pre-med student, I was fortunate enough to participate in undergraduate research with my organic chemistry professor. Just one summer in her lab motivated me to change my career goals.
After completing my master’s in chemistry at American University, I joined the Process Research department at Schering-Plough and learned the fundamentals of process development. Subsequently, Schering-Plough merged with Merck and I was presented with the opportunity to work in the Catalysis and Automation group within the Process Research department. That is where I became involved in the field of transition metal catalysis.
What is so exciting about this chemistry is that it is infinitely tunable through systematic optimization of multiple variables, making it a perfect fit for rational high throughput experimentation (HTE). This marriage of catalysis and rational HTE has the potential to significantly accelerate synthetic route development, and that allows the timely production of medicines with the potential to make a meaningful difference in patients’ lives.
What are you working on now?
My main focus is to drive adoption of HTE and automation within the pharmaceutical and academic research communities. At Merck, we believe that increased use of these techniques will fuel advances in chemistry and technology, and in turn expand the synthetic chemist’s toolbox. One way we are trying to accomplish this is by simplifying the technique. Because current HTE techniques involve multiple manual pipetting steps we are working to replace these with low-cost, widely deployable bench top automation technologies.
Of course training, communication, and collaboration are also critical. Therefore, we regularly present and publish our HTE work. Also, we are currently collaborating with David MacMillan’s group at Princeton University to optimize metallaphotoredox catalysis reactions through low-barrier 96 well HTE to drive the development and accelerate the practical application of these novel methodologies.
With regards to more advanced automation, we recently developed a tool for optimizing cryogenic, strong base mediated chemistries through automated 96 well HTE. This tool enables the rapid optimization of base, stoichiometry and temperature as well as any additional parameters of interest. Similarly, we are collaborating with Jason Hein’s group at University of British Columbia to develop an automated platform to conduct reaction progress kinetics analysis (RPKA) in high throughput. Our goal is to leverage RPKA to gain deeper insight into our screen results.
What do you anticipate working on in the future?
Flow chemistry is a rapidly advancing field in pharmaceutical process development that lends itself very well to specialty gas reactions. Currently, optimization in this area is carried out one to two reactions at a time. We are interested in developing an automated platform to optimize multiple high pressure flow reactions in parallel. The beta version of this platform has been built and the next steps will be validation of a model system followed by application to a Merck process development project.
What advice do you have for young scientists who want to make an impact using organic chemistry?
Drug discovery is an extremely challenging field; the vast majority of candidates fail to meet the necessary criteria for therapeutic use and it takes, on average, 10 years for a drug candidate to reach the market. So we as organic chemists want to ensure that synthesis is never a bottleneck.
The field has advanced to a degree that we can devise a synthesis for nearly any structure we are interested in, but we want to be able to achieve results faster than ever. And that can be accomplished by creatively leveraging new technologies. This might mean inventing a new chemical methodology, or leveraging computational chemistry to design a better catalyst, or using HTE to rapidly optimize reaction conditions.
Every inspiring accomplishment I have witnessed over the course of my career has involved embracing new technologies on multiple fronts. My advice would be to keep learning and embracing new tools as often as possible.
Is there anything else you’d like to share?
I have worked with an extremely talented and supportive group of teachers, mentors, and colleagues over my career. I have learned so much from them and found that our collaborations were the cornerstone to every success. I cannot thank and acknowledge them enough.