Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Developing effective ALS therapeutics is challenging due to the difficulty in delivering medications to the affected motor neurons in the brain, primarily because of the blood-brain barrier (BBB). The BBB, composed mainly of lipids and proteins, restricts the entry of potentially harmful substances into the central nervous system. For a molecule to permeate this barrier, it must exhibit high solubility in lipids. The Silverman laboratory has synthesized a 1,3-dione compound with potential therapeutic benefits for ALS. However, this compound faces issues of low yield and poor BBB permeability. My goal this summer is to discover an efficient synthesis strategy for the 1,3-dione and enhance its lipophilicity to improve BBB permeability. This will involve derivatizing the hydroxyl group, a relatively non-lipophilic group, with non-polar groups such as alkyls to reduce overall polarity and increase lipophilicity. The outcomes of this study will provide insights into potential structures and synthesis pathways that could lead to an effective therapeutic agent for ALS.
