Term of Award

Spring 2022

Degree Name

Master of Science, Applied Physical Science

Document Type and Release Option

Thesis (open access)

Copyright Statement / License for Reuse

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Department

Department of Chemistry and Biochemistry

Committee Chair

Brent Feske

Committee Member 1

Karelle Aiken

Committee Member 2

Mitch Weiland

Abstract

The preparation of enantiopure homopropargyl alcohols (but-3-yn-ols) is of high importance to the scientific community. They are employed as valuable pharmaceutical intermediates and are opportune to generate antiviral nucleoside analogues. Chiral inducement of these molecules thus far has been poor (low ee) and has constituted a key challenge for asymmetric synthesis in the last few decades. Enzyme-catalyzed enantioselective reductions of ketones have become popular to produce thus-prepared synthons on an industrial scale. Among them, biocatalysts (dehydrogenases, reductases) emerge as a biodegradable option for chemical transformations, in comparison to chiral catalysts that employ highly toxic metals. This research investigates the catalytic activity of a novel alcohol dehydrogenase in the enantioselective reduction of para-phenyl substituted alkynones. Through unpublished results, this enzyme exhibits unique characteristics that resolve issues of substrate insolubility with hydrophobic compounds. Due to the extensive synthetic challenges outlined in this study, much of this work focuses on the two-step synthetic strategy utilized in the preparation of putative, enzymatic starting materials. The difficulties associated with competing allenylation, and substrate instability were arduous to circumvent and contributed to low product conversion. The enzyme turned out to be the most active in the reduction of 1-(4-methoxyphenyl) hex-3-yn-one, a non-terminal acetylenic functionality, furnishing resolution products in a highly enriched form (>99% ee). Terminal propargyl functionalities proved too unstable to undergo enzymatic reduction. Subsequent steps will involve the synthesis of non-terminal propargylic ketones for enzymatic screening. The identification of reaction products was confirmed by Gas-Chromatography Mass Spectrometry (GCMS) and Nuclear Magnetic Resonance (NMR).

Research Data and Supplementary Material

No

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