Type of Document Dissertation Author Lam, Polo Chun Hung Author's Email Address email@example.com URN etd-10202004-130155 Title Experimental and Computational Studies in Bioorganic and Synthetic Organic Chemistry Degree PhD Department Chemistry Advisory Committee
Advisor Name Title Carlier, Paul R. Committee Chair Deck, Paul A. Committee Member Gandour, Richard D. Committee Member Kingston, David G. I. Committee Member Tanko, James M. Committee Member Keywords
- Memory of Chirality
- Dynamic Chirality
- Density Functional Theory
- Dynamic NMR
- Cation-Pi Interaction
- Amino Acids
- Asymmetric Synthesis
- Multivalent Binding
Date of Defense 2004-10-12 Availability mixed AbstractExperimental and Computational Studies in Bioorganic and Synthetic Organic Chemistry
Polo Chun Hung Lam
Cation–π interaction is an important determinant in protein structure and function. Among the three proteinogenic aromatic amino acids, tryptophan (Trp) is the strongest cation–π donor. We reported the asymmetric syntheses of tryptophan regioisomers in which the amino acid side chain is attached at different position of the indole moiety. These new tryptophan regioisomers can effect a different mode of cation–π interaction.
In nature, dramatic increases in binding affinity can be achieved through multivalent binding. Following a fragmentation-dimerization approach, we synthesized Taxol-based dimer in which the baccatin III core of Taxol is coupled with flexible PEG linker. However, microtubule assembly assay suggested that these new dimers are not capable of effecting bivalent binding to the Taxol binding sites in microtubules.
Memory of chirality (MOC) is an emerging theme in asymmetric synthesis in which the dynamic chirality of the reactive intermediate "memorizes" the static chirality of the reactant. Using dynamic 1D and 2D NMR and density functional theory (DFT) methods, we studied the MOC effect of 1,4-benzodiazepin-2-ones. Reconstruction of the reaction pathway using DFT calculations supported our proposed contra steric, retention of configuration mechanism.
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