Jane Eichwald, Jayme Zesiger
Timothy Beng (Chemistry)
Macrocycles are large, flexible cyclic molecules containing 11+ atoms. They are present in pharmaceuticals such as Rhazinilam (anticancer) and in naturally-derived molecules. However, their large size makes them fragile and difficult to create. Meanwhile, concerns about climate change have led to an outcry for green synthesis methods. The Environmental Protection Agency (EPA) has articulated that the use of green chemistry techniques eliminated 826 million pounds of hazardous chemicals and solvents, saved 21 billion gallons of water, and eliminated 7.8 billion pounds of carbon dioxide equivalents released to air on an annual basis. In this embodiment, the synthesis of N-macrocycles will be explored in an environmentally friendly, selective, and cost-effective way. This will be achieved through the Castagnoli-Cushman reaction, which uses commodity chemicals such as amines, aldehydes, and cyclic anhydrides. A sustainable solvent such as 2-methyltetrahydrofuran (2- Me THF) will be utilized to create a diverse library of N-macrocycles. Solvent-free and microwave-assisted synthetic routes will be evaluated. Following completion of the project, the compounds will be sent to in-house collaborators for bioactivity and toxicity studies.
Keywords: Macrocycles, Pharmaceuticals, Castagnoli-Cushman Reaction, Sustainability