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Synthesis and Biological Activity of N-Acyl Aziridines

Wells, Greggory M.
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1450458169

Abstract Details

2016, Doctor of Philosophy (PhD), Ohio University, Chemistry and Biochemistry (Arts and Sciences).
The development of new antimicrobial drugs is essential as the human population continues to build resistance to current treatments. Peptidomimetic compounds, those synthesized to mimic the behavior of naturally occurring biological proteins, have demonstrated promise in this area. Using bicyclic aziridine ring opening reactions, a library of N-acyl aziridinyl peptide isosteres has been synthesized and submitted to biological assays for cysteine protease inhibition, a common pathway to suppression of bacteria. Most of the compounds tested showed good activity against cathepsin B. This research required a novel synthetic approach to selectively generating oxazolidinones and aziridinyl ureas from fused bicyclic aziridines, which was accomplished with solvent selection, nucleophilic amine stoichiometry, and aziridine substitution. To extend the peptidic nature of these compounds, some success was achieved with acylation and amide coupling reactions. A practical approach to generating enantiomerically pure bicyclic aziridines was investigated, however the best enantioselective conditions provided only a 3 : 1 ratio. This stereoselective approach coupled with the ability to incorporate aziridines into peptide chains would ultimately lend a very powerful synthetic strategy for generating libraries of peptidomimetics with broad application potential.
Stephen Bergmeier, Ph.D. (Advisor)
Mark McMills, Ph.D. (Committee Member)
Chen Hao, Ph.D. (Committee Member)
Goetz Doug, Ph.D. (Committee Member)
283 p.
Chemistry
N-Acyl aziridine; Aziridinyl urea; Bicyclic aziridine; Cathepsin B; Asymmetric aziridination; Peptidomimetic

Recommended Citations

Citations

  • Wells, G. M. (2016). Synthesis and Biological Activity of N-Acyl Aziridines [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1450458169

    APA Style (7th edition)

  • Wells, Greggory. Synthesis and Biological Activity of N-Acyl Aziridines. 2016. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1450458169.

    MLA Style (8th edition)

  • Wells, Greggory. "Synthesis and Biological Activity of N-Acyl Aziridines." Doctoral dissertation, Ohio University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1450458169

    Chicago Manual of Style (17th edition)

ohiou1450458169
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This open access ETD is published by Ohio University and OhioLINK.