Year of Award
2015
Document Type
Dissertation
Degree Type
Doctor of Philosophy (PhD)
Degree Name
Medicinal Chemistry
Department or School/College
Department of Biomedical and Pharmaceutical Sciences
Committee Chair
Nicholas R. Natale
Commitee Members
Howard D. Beall, Donald Stierle, Keith Parker, Orion B. Berryman
Keywords
atropisomer, axial chiral, isoxazole, quadruplex, SNB19
Abstract
There are several isoxazoles in general medical practice and their metabolic fate and disposition is well known, and thus, this heterocyclic ring is often considered among the privileged scaffolds or templates for drug design and discovery. Many examples can be found of 3-aryl-isoxazoles which in theory have a chiral axis, yet actual experimental examples of direct determinations of isoxazole rotational barriers are few and far between. The dihedral angle of the 3-aryl to isoxazole bond in antibacterials of the oxacillin series increased with substitution in the 2- and 6- positions of the phenyl. Although his calculated barrier was low, this implied that atropisomers are possible for unsymmetrical substitution. The chirality of these systems differs from that of other compounds as their configuration is inverted by rotation about single bonds and can be accomplished by thermal equilibration. Thus, depending on the barrier to rotation, some of these atropisomers may only be isolated at low temperatures, if at all.
Recommended Citation
Duncan, Nathan S., "Molecular Modeling Assisted Design and Synthesis of Unsymmetrical Anthracene Isoxazole Small Molecule Anti-tumor Agents" (2015). Graduate Student Theses, Dissertations, & Professional Papers. 4619.
https://scholarworks.umt.edu/etd/4619
© Copyright 2015 Nathan S. Duncan