Type of Document	Dissertation
Author	Lam, Polo Chun Hung
Author's Email Address	plam@vt.edu
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 Microtubules Dynamic Chirality Density Functional Theory Dynamic NMR Cation-Pi Interaction Amino Acids Asymmetric Synthesis PEG Taxol Paclitaxel Multivalent Binding Tryptophan
Date of Defense	2004-10-12
Availability	mixed
Abstract Experimental and Computational Studies in Bioorganic and Synthetic Organic Chemistry Polo Chun Hung Lam ABSTRACT 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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