Moffitt Cancer Center researchers have developed a new reagent that improves the accuracy of drug synthesis. This innovative method, published in Nature Communicationspresents a novel sulfur fluoride exchange reagent (SuFEx) that enables highly controlled production of crucial sulfur-based molecules including sulfinamides, sulfonimidamides and sulfoximines.
These compounds are essential in the pharmaceutical industry, but have proven difficult to synthesize with the required stereochemical precision. The innovative t-BuSF reagent utilizes strain-release reactivity to achieve a level of efficiency and selectivity previously unattainable, paving the way for more effective drug development and broader applications in medical research.
“Sulfur-based compounds, including those developed using the new methods, are known to have favorable physicochemical properties that make them ideal candidates for drug development,” said Justin M. Lopchuk, Ph.D., senior author and associate member of Moffitt’s Department of Drug Discovery. “The ability to synthesize these compounds rapidly and stereochemically control them opens up new possibilities for designing targeted therapies that fight cancer cells more effectively while minimizing side effects.”
By taking advantage of the unique properties of the t-BuSF reagent, researchers were able to explore previously inaccessible chemical space within the sulfur family, particularly in the S(IV) and S(VI) oxidation states. This breakthrough has resulted in the creation of more than 70 new chemical compounds, many of which have immediate applications in medicinal chemistry and the development of new pharmaceutical agents.
Lopchuk adds that this research has already been used to significantly improve the scalable synthesis of DFV890, an investigational Novartis compound currently in clinical trials at Moffitt and elsewhere for myeloid diseases.