Synthetic Investigation of Natural Products Causing Dopaminergic Neurodegeneration
by
 
Cunningham, Michael John, author.

Title
Synthetic Investigation of Natural Products Causing Dopaminergic Neurodegeneration

Author
Cunningham, Michael John, author.

ISBN
9780438068285

Personal Author
Cunningham, Michael John, author.

Physical Description
1 electronic resource (136 pages)

General Note
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
 
Advisors: John Rimoldi Committee members: David Colby; Jared Delcamp; Robert Doerksen.

Abstract
The terrestrial organisms Streptomyces venezuelae and Rhaponticum repens produce toxic secondary metabolites that likely function as chemical deterrents. The polyketide SV-6 from S. venezuelae and the sesquiterpene lactone repin from R. repens both produce dose-dependent and selective degeneration of dopaminergic neurons. These molecules represent two possible tools that can be used to explore chemotoxic induction of Parkinson's disease. In the case of SV-6, a newly isolated metabolite, total synthesis was undertaken to confirm its structure and biological activity. The natural product was produced from methacrolein and Roche ester starting materials that were elaborated to their respective fragments, a vinyl iodide and a Weinreb amide. These fragments were coupled to form SV-6 and the synthesis allows for many additional opportunities to easily generate stereoisomers and analogs for further study. In the case of repin, previously isolated material was used as a starting material to create a biotin-labeled probe. There were considerable challenges due to the electrophilic nature of the compound, but a Nicolas reaction followed by copper catalyzed cycloaddition produced an impure biotin-repin probe. Repin was also subjected to screening in multiple biological assays which identified proteins potentially responsible for its neurodegenerative activity.

Local Note
School code: 0131

Subject Term
Pharmaceutical sciences.

Added Corporate Author
The University of Mississippi. Medicinal Chemistry.

Electronic Access
http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:10814724


Shelf NumberItem BarcodeShelf LocationShelf LocationHolding Information
XX(681141.1)681141-1001Proquest E-Thesis CollectionProquest E-Thesis Collection