Synthesis of Molecular Tools and Evaluation of Dirhodium Catalyst Conformations

In this thesis, topics ranging from synthetic organic chemistry to computational DFT studies have been explored. For the first project, photocaged enzyme substrates were synthesized to be used in crystallographic studies of the enzyme PmHMGR. This includes a novel asymmetric synthesis of mevalonic acid stereoisomers. The photophysical properties of caged substrates were explored from both an experimental and computational approach. Preliminary crystallographic experiments have been carried out which indicate possible stability issues of the caged compounds within the crystal environment. A control compound was synthesized and crystallographic efforts are ongoing. For the second project, a novel cholesterol mimic was synthesized to be used for studying cholesterol cellular trafficking. This compound has been made available to the broader research community. An additional project involves the scale up of potential NPC drug CP2. The compound was synthesized and efforts to scale up the drug candidate are discussed. The final two projects involve DFT studies. Conformation energetics of dirhodium paddle wheel complexes were evaluated computationally. For a system involving a psuedoarmoatic ligand scaffold, known as Rh2(Pro-SqEB)4, the C4 conformation was found to be the lowest energy conformer. Additionally, a heteroleptic system, known as Rh2(S-PTTL)2(1S,2R-DPPhTCB)2, was studied with a thioether coordinating group. Cis/trans configurations were evaluated along with a conformational study and the nature of the thioether was assessed. An ether variation was proposed as a synthetic target for future direction and the energetics of this complex were assessed. For the second DFT study, oxazolidinone was evaluated as a directing group for palladium catalyzed concerted metalation deprotonation on an aromatic ring. Results indicated that each heteroatomic site of oxazolidinone was a poor director for the system studied. Oxazolidinthione was evaluated in place of oxazolidinone and was found to be a better directing group but did not outcompete undirected concerted metalation deprotonation.