Title page for ETD etd-10202004-130155


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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