Total synthesis of all (−)-agelastatin alkaloids
The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family that possess a tetracyclic molecular framework incorporating C4–C8 and C7–N12...
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| Format: | Article |
| Language: | en_US |
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Royal Society of Chemistry, The
2013
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| Online Access: | http://hdl.handle.net/1721.1/82461 https://orcid.org/0000-0003-3080-1063 |
| _version_ | 1826191370235150336 |
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| author | Movassaghi, Mohammad Siegel, Dustin S. Han, Sunkyu |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Movassaghi, Mohammad Siegel, Dustin S. Han, Sunkyu |
| author_sort | Movassaghi, Mohammad |
| collection | MIT |
| description | The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family that possess 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 all known agelastatin alkaloids including the first total syntheses of agelastatins C, D, E, and F. 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. |
| first_indexed | 2024-09-23T08:54:52Z |
| format | Article |
| id | mit-1721.1/82461 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:54:52Z |
| publishDate | 2013 |
| publisher | Royal Society of Chemistry, The |
| record_format | dspace |
| spelling | mit-1721.1/824612022-09-26T09:08:07Z Total synthesis of all (−)-agelastatin alkaloids Movassaghi, Mohammad Siegel, Dustin S. Han, Sunkyu Massachusetts Institute of Technology. Department of Chemistry Movassaghi, Mohammad Siegel, Dustin S. Han, Sunkyu The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family that possess 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 all known agelastatin alkaloids including the first total syntheses of agelastatins C, D, E, and F. 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. National Institute of General Medical Sciences (U.S.) (GM074825) Amgen Inc. AstraZeneca (Firm) Bristol-Myers Squibb Company DuPont (Firm) Alfred P. Sloan Foundation (Research Fellowship) 2013-11-18T19:56:54Z 2013-11-18T19:56:54Z 2010-08 2010-07 Article http://purl.org/eprint/type/JournalArticle 2041-6520 2041-6539 http://hdl.handle.net/1721.1/82461 Movassaghi, Mohammad, Dustin S. Siegel, and Sunkyu Han. “Total synthesis of all (−)-agelastatin alkaloids.” Chemical Science 1, no. 5 (2010): 561. https://orcid.org/0000-0003-3080-1063 en_US http://dx.doi.org/10.1039/c0sc00351d Chemical Science Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Royal Society of Chemistry, The PMC |
| spellingShingle | Movassaghi, Mohammad Siegel, Dustin S. Han, Sunkyu Total synthesis of all (−)-agelastatin alkaloids |
| title | Total synthesis of all (−)-agelastatin alkaloids |
| title_full | Total synthesis of all (−)-agelastatin alkaloids |
| title_fullStr | Total synthesis of all (−)-agelastatin alkaloids |
| title_full_unstemmed | Total synthesis of all (−)-agelastatin alkaloids |
| title_short | Total synthesis of all (−)-agelastatin alkaloids |
| title_sort | total synthesis of all agelastatin alkaloids |
| url | http://hdl.handle.net/1721.1/82461 https://orcid.org/0000-0003-3080-1063 |
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