A Combinatorial and Solution Phase Approach to the Synthesis of Polyyne Compound Libraries with Therapeutically Relevant Biological Activity.
Date Thesis Awarded
Honors Thesis -- Open Access
Bachelors of Science (BS)
Robert J. Hinkle
Douglas D. Young
As antibiotic resistant infections continue to grow and pharmaceutical research in antibiotics continues to subside, the search for novel antibiotic agents in academia research is urgent. In this respect, an attractive class of natural products with known antibiotic properties that spans animals, plants, and fungi and operates via many mechanisms of action are the polyacetylenes (polyynes). To elucidate the underlying structural principles that are at the foundation of the potent bioactivity of the polyynes, we first synthesized a library of diynols that are structurally alike to an antifungal, antibacterial, and anticancer diynol natural product, and subsequently tested our diynol products on E. coli and P. fluorescens bacterial cells lines. To bypass the synthetic challenges that have historically restricted polyyne therapeutic research, we employed a novel combined approach of combinatorial (solid-supported) and solution phase chemistries to produce the library efficiently and rapidly. We then took the major biologically potent compounds from these screenings and synthetically modified their peripheral functional groups to further deduce the link between polyyne structure at the molecular level and polyyne activity at the observable level.
Funk, Cody, "A Combinatorial and Solution Phase Approach to the Synthesis of Polyyne Compound Libraries with Therapeutically Relevant Biological Activity." (2023). Undergraduate Honors Theses. William & Mary. Paper 1979.
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