Matching Items (2)
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- All Subjects: Chemistry, Organic
- Creators: Skibo, Edward
Description
Throughout time, compounds from natural sources have provided humans with medicines, and recently become the structural inspiration for semisynthetic drugs. One arena that has benefited greatly from the use of these natural products is the discovery of novel antibacterial agents. Methicillin-resistant Staphylcoccus aureus (MRSA) continues to plague the United States as well as throughout the world, at least in part because of increasing antibiotic resistance. Therefore, scientists continue to scour natural products as potential leads, either directly or indirectly, for antibiotics to treat MRSA. The structure of the indole sesquiterpene, polyalthenol, was discovered in 1976 and recent work shows a 4µg/mL minimum inhibitory concentration (MIC) against a variety of strains of MRSA. Given the unique framework of this natural product and its biological activity against MRSA, the total synthesis becomes the next logical step. Presently a racemic synthesis has successfully afforded an indole ketone with the correct relative stereochemistry of polyalthenol, however, the completion of the total synthesis of polyalthenol presents several challenges. Herein, the work towards the synthesis is described in addition to the proposed completion of the synthesis.
ContributorsReichenberg, Erynn Wright (Author) / Madar, David J (Thesis advisor) / Skibo, Edward (Committee member) / Miller, William (Committee member) / Arizona State University (Publisher)
Created2012
Description
Combretastatin A-4 (CA-4) represents one of the most promising antineoplastic and cancer vascular targeting stilbenes that have been isolated from the South African bush willow, Combretum Caffrum Kuntze. In order to further explore the bioactivity of this molecule, a diiodo derivative of CA-4, as well as its phosphate prodrug, was synthesized and analyzed for its biological activity; although only a scale up synthesis of this compound was performed herein for ongoing analysis. In general, no increased specificity was noted for the human cancer cell lines. Antiangiogenic properties were similar to the untreated control. The diiodocombstatin was active against M. luteus, and its phosphate prodrugs were very active against N. gonorrhoeae. Combretastain A-2 is another biologically active stilbene isolated from Combretum Caffrum Kuntze. In an attempt to increase biological activity of this molecule both mono-iodo and diiodo derivatives have been partially synthesized. The initial step involving the iodination of piperonal utilizes a novel, cost effective and mild reaction. The iodo stilbenes were obtained via a Wittig reaction using phosphonium salts 25 and 27 along with 2,3-Bis-[tert-butyldimethylsiloxy]-4-methoxy benzaldehyde 29. Deprotection of the subsequent z-stilbenes, non-isolated mono-iodo stilbene and the diiodo 30 produced two synthetic objective z-stilbenes 16 and 17. Synthesis as well as biological analysis is ongoing.
ContributorsTrickey-Platt, Brindi Brooks (Author) / Pettit, George R. (Thesis advisor) / Moore, Ana (Committee member) / Skibo, Edward (Committee member) / Arizona State University (Publisher)
Created2011