Document Type
Thesis
Date of Degree Completion
Spring 2024
Degree Name
Master of Science (MS)
Department
Chemistry
Committee Chair
Dr. Timothy K. Beng
Second Committee Member
Dr. Gil Belofsky
Third Committee Member
Dr. Levente Fabry-Asztalos
Abstract
Functionalized tetrahydropyrans are structural motifs in diverse natural products, including polyether antibiotics, marine toxins, pheromones, and pharmaceuticals. They are frequently used as versatile building blocks for accessing stereochemically sophisticated biologically active compounds. Specifically, functionalized bicyclic tetrahydropyrans bearing contiguous stereocenters have garnered interest in the synthesis and medicinal chemistry communities. Thus far, some synthetic methods have been developed for their construction and functionalization. These methods include Prins' cyclization reactions, intramolecular oxa-Michael reactions, hetero-Diels-Alder cyclization, ring-closing metathesis, radical cyclization, and halocycloetherification. However, these methods have some drawbacks such as the need for expensive reagents and catalysts, substrate limitations, and environmentally unfriendly conditions. Seeking to develop a new strategy to produce lactam-fused tetrahydropyrans, we successfully designed a modular, cost-saving, transition metal-free, and environmentally friendly approach that leverages the 1,3-azadiene-anhydride annulation reaction. Suitable reaction conditions were successfully investigated for the halocycloetherification of trisubstituted lactam-bearing tertiary alkenols to access bicyclic tetrahydropyrans in good yields, regioselectivities, and diastereoselectivities. The requisite bromoethers were then engaged efficiently in a dehydrobromination protocol, leading to the syntheses of highly substituted lactam-tethered 3-methylenetetrahydropyrans, which are highly prevalent in pharmaceuticals and materials. We anticipate that this versatile synthetic method will be embraced by the organic and medicinal chemistry communities. We have laid the foundation for a future structure-activity relationship (SAR) study through collaborative efforts. The ultimate goal is to find new therapeutics for several diseases, including diabetes mellitus.
Recommended Citation
Anosike, Ifeyinwa Stella, "Stereocontrolled Synthesis of Lactam-fused Tetrahydropyrans as Potential Antidiabetic Agents" (2024). All Master's Theses. 1933.
https://digitalcommons.cwu.edu/etd/1933