Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010.
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
| Published: |
Massachusetts Institute of Technology
2011
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/60817 |
| _version_ | 1826215922716639232 |
|---|---|
| author | Siegel, Dustin S. (Dustin Scott), 1980- |
| author2 | Mohammad Movassaghi. |
| author_facet | Mohammad Movassaghi. Siegel, Dustin S. (Dustin Scott), 1980- |
| author_sort | Siegel, Dustin S. (Dustin Scott), 1980- |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. |
| first_indexed | 2024-09-23T16:39:11Z |
| format | Thesis |
| id | mit-1721.1/60817 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T16:39:11Z |
| publishDate | 2011 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/608172019-04-12T13:36:50Z Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins Total synthesis of acylfulvene, and irofulven Total synthesis of the agelastatin alkaloids Siegel, Dustin S. (Dustin Scott), 1980- Mohammad Movassaghi. Massachusetts Institute of Technology. Dept. of Chemistry. Massachusetts Institute of Technology. Dept. of Chemistry. Chemistry. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010. Vita. Cataloged from PDF version of thesis. Includes bibliographical references. I. Enantioselective Total Synthesis of (-)-Acylfulvene, and (-)-Irofulven We report the enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven, which features metathesis reactions for the rapid assembly of the molecular framework of these anti tumor agents. We discuss (1) the application of an Evans Cu-catalyzed aldol addition reaction using a strained cyclopropyl ketene thioacetal, (2) an efficient enyne ring-closing metathesis cascade reaction in a challenging setting, (3) the reagent, IPNBSH, for a late stage reductive allylic transposition reaction, and (4) the final ring-closing metathesis/dehydrogenation sequence for the formation of (-)-acylfulvene and (-)-irofulven. II. Total Synthesis of the (-)-Agelastatin Alkaloids The pyrrole-imidazole super-family of marine alkaloids, derived from linear clathrodinlike precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family that have a tetracyclic molecular framework incorporating C4-C8 and C7-N12 bond connectivities. We provide a hypothesis for the formation of the unique agelastatin architecture that maximally exploits the intrinsic chemistry of plausible biosynthetic precursors. We report the concise enantioselective total syntheses of the agelastatin alkaloids, including the first total syntheses of agelastatins C and E. Our gram-scale chemical synthesis of agelastatin A was inspired by our hypothesis for the biogenesis of the cyclopentane C-ring and required the development of new transformations including an imidazolone-forming annulation reaction and a carbohydroxylative trapping of imidazolones. by Dustin S. Siegel. Ph.D. 2011-01-26T14:29:27Z 2011-01-26T14:29:27Z 2010 2010 Thesis http://hdl.handle.net/1721.1/60817 696796006 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 285 p. application/pdf Massachusetts Institute of Technology |
| spellingShingle | Chemistry. Siegel, Dustin S. (Dustin Scott), 1980- Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins |
| title | Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins |
| title_full | Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins |
| title_fullStr | Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins |
| title_full_unstemmed | Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins |
| title_short | Enantioselective total syntheses of acylfulvene, irofulven, and the agelastatins |
| title_sort | enantioselective total syntheses of acylfulvene irofulven and the agelastatins |
| topic | Chemistry. |
| url | http://hdl.handle.net/1721.1/60817 |
| work_keys_str_mv | AT siegeldustinsdustinscott1980 enantioselectivetotalsynthesesofacylfulveneirofulvenandtheagelastatins AT siegeldustinsdustinscott1980 totalsynthesisofacylfulveneandirofulven AT siegeldustinsdustinscott1980 totalsynthesisoftheagelastatinalkaloids |