Development and application of synthetic methods that enable medicinal research

The development of modern pharmaceuticals relies heavily upon the drug discovery process to uncover new molecular entities able to modulate disease states. Integral to this process is the ability of scientists to quickly synthesize analogues of a hit or lead compound to improve critical qualities. Ease of synthesis is directly related to existing methodologies which facilitate key chemical transformations necessary to assemble potential drug molecules. In this thesis, a medicinal chemistry program is described that relies on the well-established Suzuki-Miyaura coupling to assemble small molecule inhibitors of protein arginine methyl transferase 4, a potential target for cancer therapy. Significant advances are made towards obtaining a potent, selective, and cell-active pharmacological probe. A concise synthesis of the therapeutic 1-deoxygalactonojirimycin is also described, which utilizes a tandem α-chlorination aldol reaction developed by the Britton group to install several stereocenters in one step. In addition, a novel route to access enantioenriched acid-sensitive α-substituted aldehydes via a bench-stable intermediate was investigated.