Dr. Soumitra V. Athavale, hailing from Pune, India, embarked on his academic journey with a fervent passion for the intersection of chemistry and biology. His formative years were spent at the prestigious Indian Institute of Science Education and Research (IISER) Pune, where he honed his skills under the mentorship of Prof. Harinath Chakrapani and Prof. Sanjeev Galande, delving deep into the realms of organic chemistry and molecular biology. Subsequently, he ventured across continents and joined the distinguished group of Prof. Scott Denmark at the University of Illinois, Urbana-Champaign, for his doctoral pursuits. There, Dr. Athavale’s research delved into the intricacies of organic synthesis and mechanistic pathways in asymmetric autocatalytic reactions, notably the Soai reaction. His academic journey culminated with his current position as a postdoctoral scholar in the esteemed lab of Prof. Frances Arnold at Caltech, where he has been pushing the frontiers of synthetic nitrene chemistry through innovative applications of hemeproteins. Driven by a profound fascination for asymmetric catalysis, biocatalysis, and molecular evolution, particularly within complex systems, Dr. Athavale stands as a dedicated and promising figure in the field of chemical research.
Recently, I was announced as the cowinner of the Merck Compound Challenge 2020. The other winning team was a 10-member group from the Max Planck Institute, Germany. We share the euro 10000 winning prize.
The Merck Compound Challenge is an annual competition to propose a synthetic route towards a small molecule natural product. Within just two years of its inception, the Compound Challenge has positioned itself as a highly prestigious global event where teams assembled from among the foremost organic chemistry research groups in academia compete for the top prize.
The competition is open to anyone in the world and participation can be as a team or an individual. For the 132 teams participating this year, the small molecule structure – Melangenoterpenes A was released on 14 Feb and the teams had 96 hours to come up with a retrosynthesis with experimental details. To select the finalists, each team scored the proposal of 6-8 other teams in a double-blind pairing.
The top 10 teams with the highest scores were selected for the next round, where their routes were executed in the lab by a CRO. This is where the experimental protocols described in the initial submission mattered. The synthesis was done in a single attempt by following these protocols without any optimization. The route that went furthest towards the target was to be declared as the winner (and recipient of the 10000 euro prize). Amazingly, both the winning teams had a nearly identical route which included a Diels-Alder reaction as the key disconnect. The strategy allowed rapid access to the main spirocyclic core of the target within 5 steps, in an enantioselective manner.
As an organic chemist, this is something I will forever cherish! My main motivation to participate was to see how my proposal would compare with the best in the world. As an individual participant, the 96-hour timeframe is very constraining and having more members helps to quickly process ideas in parallel. One has to think about multiple routes and then critically analyze the weaknesses of each one. The winning route that I came up with was formulated in the last 36 hours of my time, including the detailed write-up – the challenge was an exhilarating experience mentally and physically.
There was no special preparation. Such competitions are a test of the long-term knowledge and expertise one has gained over their career. I made sure that I had on hand key textbooks and model sets for quick reference. However good the route is on paper, it is difficult to guess how it will perform in the lab, especially without optimizations. I am lucky the route was ultimately successful.
I have been fortunate to have been mentored by extraordinary scientists right from my undergraduate days in IISER Pune to PhD at UIUC and now postdoc at Caltech. I dedicate this win to all those mentors. During my PhD in Prof. Denmark’s group, we had a similar event called “Molecule of the Month” in October, when the research group was divided into three teams, given the structure of a recently reported complex natural product and challenged to come up with a retrosynthetic route to the target molecule and present their solutions. This was a critical aspect of organic chemistry training and provided a rigorous exercise in identifying the constituents of a good synthetic plan. Every year, I used to be very excited about this event and the recurring experience undoubtedly proved invaluable in coming up with a competent proposal in the Merck Challenge.
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