KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Metal-Templated Assembly of Heterocyclic Rings via Nucleophilic Cyclization of Cyclopropenes

    Thumbnail
    View/Open
    Maslivetc_ku_0099D_16474_DATA_1.pdf (6.747Mb)
    Issue Date
    2019-05-31
    Author
    Maslivetc, Vladimir
    Publisher
    University of Kansas
    Format
    245 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Chemistry
    Rights
    Copyright held by the author.
    Metadata
    Show full item record
    Abstract
    This thesis is focused on the development and application of methods for the intramolecular nucleophilic addition of tethered nucleophiles to cyclopropenes. Addition of carbon-, nitrogen, and oxygen-nucleophiles was demonstrated to provide access to γ-aminobutyric acid (GABA) derivatives and biologically relevant cyclopropane-fused heterocyclic rings (heteroazepanones, heteroazocanones, and pyrrolidinones). The thesis is divided into five chapters, which discuss not only the development and elaboration of our chemistry, but also biological importance and alternative methods for synthesis of target heterocycles presented in literature. Chapter one is a review of biological activity, occurrence in nature, and synthetic approaches for the preparation of heteroazepanones and heteroazocanones. The chapter will describe methods based on cyclization and ring expansion reactions, as well as multicomponent and tandem methods. Chapter two focuses on the one-pot synthesis of various γ-aminobutyric acid (GABA) amides through unassisted nucleophilic addition of primary and secondary amines across the double bond of cyclopropene-3-carboxamides. Initial nucleophilic attack is followed by a ring opening of the resulting donor-acceptor cyclopropanes. Subsequent in situ reduction of enamine or imine intermediates allows to access substituted GABA derivatives. Chapter three describes a formal intramolecular nucleophilic substitution reaction of bromocyclopropanes with nitrogen ylides generated in situ from N-benzyl carboxamides. This reaction represents the 5-exo-trig cyclization through intermolecular base-assisted nucleophilic addition of tethered benzylic anion to cyclopropenes generated in situ by dehydrohalogenation of bromocyclopropanes. Chapter four describes modular assembly of enantiopure cyclopropane-fused oxazepanones through a strain-release-driven, cation-templated intramolecular nucleophilic addition of tethered alkoxides to prochiral cyclopropenes. The mechanism of enantiomeric induction is detailed. The biological profile exhibited by some of obtained 2-oxa-5-azabicyclo[5.1.0]octan-6-ones is characterized by promising activity against Mycobacterium abscessus coupled with apparent low general toxicity against cultured human cells. The final chapter covers ring-retentive 7- and 8-exo-trig nucleophilic attack of tethered nitrogen-based nucleophiles at cyclopropene double bond. The described potassium-templated cyclization proceeds in highly regio- and diastereoselective fashion and provides expedited access to previously unknown drug-like scaffolds including several structures with promising anti-cancer properties.
    URI
    http://hdl.handle.net/1808/29889
    Collections
    • Chemistry Dissertations and Theses [336]
    • Dissertations [4318]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps