• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of TUScholarShareCommunitiesDateAuthorsTitlesSubjectsGenresThis CollectionDateAuthorsTitlesSubjectsGenres

    My Account

    LoginRegister

    Help

    AboutPoliciesHelp for DepositorsData DepositFAQs

    Statistics

    Display statistics

    NATURAL PRODUCT ANALOGUES AND 2-PYRIDONE PHOTOCHEMISTRY

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    TETDEDXRossiter-temple-0225E-1 ...
    Size:
    32.55Mb
    Format:
    PDF
    Download
    Genre
    Thesis/Dissertation
    Date
    2020
    Author
    Rossiter, Lauren Michele
    Advisor
    Sieburth, Scott McNeill
    Committee member
    Andrade, Rodrigo B.
    Wang, Rongsheng
    Cannon, Kevin C.
    Department
    Chemistry
    Subject
    Chemistry, Organic
    2-pyridone
    Natural Product Analogue
    Photochemistry
    Promysalin Analogues
    Sila-albocycline
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/3496
    
    Metadata
    Show full item record
    DOI
    http://dx.doi.org/10.34944/dspace/3478
    Abstract
    There is a profound need for new antibiotics which overcome bacterial resistance. The predominant source for these is natural products; however, they are often quickly rendered ineffective due to antibiotic resistance. A proven method in drug discovery is improving the properties of natural products through diverted total synthesis (DTS). Of particular interest is promysalin, which is produced by Pseudomonas putida, and selectively inhibits the growth of Gram-negative pathogenic bacteria Pseudomonas aeruginosa at nanomolar concentrations. The work herein describes modifications to the side chain which were shown to modulate antibacterial potency and specificity. A similarly inspired approach to countering antibiotic resistance is the targeted modification of a single carbon to silicon, motivated by the proven success of this substitution shown in pharmaceuticals and amino acids. The target for this modification is albocycline, a known macrolactone antibiotic that exhibits potent antibiotic activity against S. aureus. Replacing the C4 carbon of albocycline with silicon will provide sila-albocycline with enhanced hydrogen bonding properties and altered lipophilicity due to the slight changes from the carbon to silicon atom. In addition, there is anticipated intrinsic stability of the silanol toward rearrangement reactions than carbon-based. The proposed synthesis diverts from the known total synthesis of albocycline, as reported by the Andrade Group. This work details the efforts made towards the total synthesis of sila-albocycline. Lastly, there is untapped potential for UV-promoted photochemistry to create molecular scaffolds, which may lead to novel synthetic routes to complex molecules in addition to providing new polycycles that may expand current medicinal products. The work herein describes the synthesis of tethered chloro- and methoxy-substituted benzyl alcohols to 2-pyridones and the resulting products when exposing the solution to ultraviolet light. This generated new polycycles with complex structures which have unexplored biological or medicinal properties.
    ADA compliance
    For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Temple University Libraries | 1900 N. 13th Street | Philadelphia, PA 19122
    (215) 204-8212 | scholarshare@temple.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.