Experimental and Computational Studies in Bioorganic and Synthetic Organic Chemistry

Cationâ Ï interaction is an important determinant in protein structure and function. Among the three proteinogenic aromatic amino acids, tryptophan (Trp) is the strongest cationâ Ï 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 cationâ Ï 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.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Department dc:contributor.department

Chemistry

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2004

Author dc:creator

• Lam, Polo Chun Hung

Chair dc:contributor.committeechair

• Carlier, Paul R.

Committee members dc:contributor.committeemember

• Tanko, James M.
• Gandour, Richard D.
• Deck, Paul A.
• Kingston, David G. I.

• Memory of Chirality
• Microtubules
• Dynamic Chirality
• Density Functional Theory
• Dynamic NMR
• Cation-Pi Interaction
• Amino Acids
• Asymmetric Synthesis
• PEG
• Taxol
• Paclitaxel
• Multivalent Binding
• Tryptophan

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

etd-10202004-130155

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/40013