Abstract
In the first part of this dissertation (chapters 1-4) we discuss the development of bimetallic and monometallic palladium complexes scaffolded on 2-phosphinoimidazole ligands and their application to cross-coupling reactions. Specifically, we discovered a bimetallic Pd(II) dimer that performs a tandem arylation/annulation reaction to produce naphthalene products from aryl iodides and ketones (Chapter 2). We then show that bimetallic Pd(II) and Pd (I) complexes have different activity in different transformations and that the starting oxidation state of our catalysts is important for reactivity (Chapter 3). For example, we demonstrate that our Pd(I) dimer is much more active in Buchwald- Hartwig amination reactions than is the Pd(II) dimer. However, in aminocarbonylation reactions of aryl halides, the Pd (II) dimer has a better activity than the Pd (I) dimer. Finally, we demonstrate that when our 2-phosphinoimidazole ligand is modified to contain P-t-Bu groups rather than P-Ph groups, monometallic P-N coordinated compounds are obtained (Chapter 4). These monometallic complexes are highly active in Buchwald-Hartwig amination reactions with less reactive aryl chloride substrates. Importantly, favoring the formation of a monomer is essential for catalysis, where ligands that form bimetallic complexes of Pd are not active in this cross-coupling reaction with aryl chlorides. The second part of this thesis focuses on the development of peptide-based catalysts for enantioselective synthesis. We demonstrate that a 14-amino acid helical peptide containing two catalytic groups can engage in cooperative catalytic reactions. In addition, crafting the chiral environment on the peptide backbone can enable highly enantioselective nitroolefin addition reactions. In Chapter 6, due to our experience in peptide synthesis, we developed an advanced undergraduate laboratory protocol for solid phase synthesis of a 3 amino acid peptide. This lab enables undergraduate students to develop skills in the synthesis, purification, and identification (using advanced 1D and 2D NMR techniques) of polypeptides. Finally, in Chapter 7, we described our efforts to develop Protease Targeting Chimeras (PROTACs) for selective protein degradation of Sphk1 and Sphk2 in pancreatic cancer cell lines. We synthesized a library of different PROTACs with different linkers with different lengths that include the aliphatic carbon chains, PEG chains, and heterocycle-containing tethers. Our PROTAC design included the incorporation of different inhibitors that are selective for either Sphk1 or Sphk1.
Degree
PhD
College and Department
Computational, Mathematical, and Physical Sciences; Chemistry and Biochemistry
Rights
https://lib.byu.edu/about/copyright/
BYU ScholarsArchive Citation
Rodriguez Moreno, Mariur, "Design and Synthesis of Bimetallic Catalyst and Multifunctional Peptide Catalysis for Organic Synthesis and Synthesis of Proteolysis Targeting Chimeras (PROTACs) for Sphk1 and Sphk2" (2024). Theses and Dissertations. 10724.
https://scholarsarchive.byu.edu/etd/10724
Date Submitted
2024-12-13
Document Type
Dissertation
Handle
http://hdl.lib.byu.edu/1877/etd13560
Keywords
Bimetallic catalysis, monometallic, Palladium, dimer, organometallics, peptides, catalysis, cooperative reactions, small molecules, PROTAC, Sphingosine Kinase 1, Sphingosine Kinase 2
Language
english