Synthetic efforts toward the natural products (-)-verrucarol and psiguadial A & aniline N-oxide functionalization
| Author(s) | Wisthoff, Michael Francis | |
| Date Accessioned | 2018-05-16T11:27:23Z | |
| Date Available | 2018-05-16T11:27:23Z | |
| Publication Date | 2017 | |
| SWORD Update | 2018-02-20T20:41:28Z | |
| Abstract | The first project involves our efforts toward the core structure of the macrocyclic trichothecene (–)-verrucarol (3). We developed a short synthetic concept for the enantioselective synthesis of the natural product. The key step is an asymmetric intramolecular Mizoroki-Heck reaction. In order to evaluate the key step, we synthesized several substrates and screened various reaction conditions. ☐ The second project involves the discovery of a method for the functionalization of aniline-N-oxides. Discovery of the method took place while searching for a general method for the generation of aza-ortho-xylylenes in situ. We found the reaction to be quite general, allowing us to access aminophenols, aminoarylsulfonates, alkylated anilines, and aminoanilines in 29−95% yield in a single laboratory operation from easily isolable, bench-stable N,N-dialkylaniline N-oxides. ☐ The final project involves our efforts toward the total synthesis of the meroterpenoid psiguadial A (190). The key step is an enolate–ortho-quinone methide (o-QM) reaction followed by an oxa-Michael addition to form the seven-member heterocyclic ring. The first generation synthesis toward the terpene derived silyl enol ether (225) was investigated. In an effort to better understand and optimize the two key steps in the synthesis, a model system of psiguadial A (190) was developed. We successfully synthesized the product of the enolate–o-QM reaction, that is, the keto phenol (254A). Evaluation of the oxa-Michael reaction, did not return the desired products. Several synthetic strategies were developed and implemented, but did not lead to the seven-member heterocyclic ring. Current efforts involve the synthesis of intermediates of form the seven-member heterocycle to form the via copper-catalyzed C-O coupling. A second generation of the silyl enol ether (225) is also being investigated and addresses the major problems of the first generation’s synthetic challenges. | en_US |
| Advisor | Chain, William J. | |
| Degree | Ph.D. | |
| Department | University of Delaware, Department of Chemistry and Biochemistry | |
| Unique Identifier | 1035762508 | |
| URL | http://udspace.udel.edu/handle/19716/23168 | |
| Language | en | |
| Publisher | University of Delaware | en_US |
| URI | https://search.proquest.com/docview/2023453294?accountid=10457 | |
| Keywords | Pure sciences | en_US |
| Keywords | (–)-Verrucarol | en_US |
| Keywords | Aniline N-oxide functionalization | en_US |
| Keywords | Natural products | en_US |
| Keywords | Psiguadial A | en_US |
| Keywords | Synthetic efforts | en_US |
| Title | Synthetic efforts toward the natural products (-)-verrucarol and psiguadial A & aniline N-oxide functionalization | en_US |
| Type | Thesis | en_US |