Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines
The enantioselective total synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine B, (-)-quadrigemine C, and (-)-psycholeine through a diazene-directed assembly of cyclotryptamine fragments is described. Our synthetic strategy enables multiple and directed assembly of intact cyclotryptamine...
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125956 |
| _version_ | 1826192641482555392 |
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| author | Lindovska, Petra Movassaghi, Mohammad |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Lindovska, Petra Movassaghi, Mohammad |
| author_sort | Lindovska, Petra |
| collection | MIT |
| description | The enantioselective total synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine B, (-)-quadrigemine C, and (-)-psycholeine through a diazene-directed assembly of cyclotryptamine fragments is described. Our synthetic strategy enables multiple and directed assembly of intact cyclotryptamine subunits for convergent synthesis of highly complex bis- and tris-diazene intermediates. Photoextrusion of dinitrogen from these intermediates enables completely stereoselective formation of all C3a-C3a′ and C3a-C7′ carbon-carbon bonds and all the associated quaternary stereogenic centers. In a representative example, photoextrusion of three dinitrogen molecules from an advanced intermediate in a single-step led to completely controlled introduction of four quaternary stereogenic centers and guided the assembly of four cyclotryptamine monomers en route to (-)-quadrigemine C. The synthesis of these complex diazenes was made possible through a new methodology for synthesis of aryl-alkyl diazenes using electronically attenuated hydrazine-nucleophiles for a silver-promoted addition to C3a-bromocyclotryptamines. The application of Rh- and Ir-catalyzed C-H amination reactions in complex settings were used to gain rapid access to C3a- and C7-functionalized cyclotryptamine monomers, respectively, used for diazene synthesis. This convergent and modular assembly of intact cyclotryptamines offers the first solution to access these alkaloids through completely stereoselective union of monomers at challenging linkages and the associated quaternary stereocenters as illustrated in our synthesis of five members of the oligocyclotryptamine family of alkaloids. |
| first_indexed | 2024-09-23T09:26:59Z |
| format | Article |
| id | mit-1721.1/125956 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:26:59Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1259562022-09-30T14:28:08Z Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines Lindovska, Petra Movassaghi, Mohammad Massachusetts Institute of Technology. Department of Chemistry The enantioselective total synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine B, (-)-quadrigemine C, and (-)-psycholeine through a diazene-directed assembly of cyclotryptamine fragments is described. Our synthetic strategy enables multiple and directed assembly of intact cyclotryptamine subunits for convergent synthesis of highly complex bis- and tris-diazene intermediates. Photoextrusion of dinitrogen from these intermediates enables completely stereoselective formation of all C3a-C3a′ and C3a-C7′ carbon-carbon bonds and all the associated quaternary stereogenic centers. In a representative example, photoextrusion of three dinitrogen molecules from an advanced intermediate in a single-step led to completely controlled introduction of four quaternary stereogenic centers and guided the assembly of four cyclotryptamine monomers en route to (-)-quadrigemine C. The synthesis of these complex diazenes was made possible through a new methodology for synthesis of aryl-alkyl diazenes using electronically attenuated hydrazine-nucleophiles for a silver-promoted addition to C3a-bromocyclotryptamines. The application of Rh- and Ir-catalyzed C-H amination reactions in complex settings were used to gain rapid access to C3a- and C7-functionalized cyclotryptamine monomers, respectively, used for diazene synthesis. This convergent and modular assembly of intact cyclotryptamines offers the first solution to access these alkaloids through completely stereoselective union of monomers at challenging linkages and the associated quaternary stereocenters as illustrated in our synthesis of five members of the oligocyclotryptamine family of alkaloids. NIH-NIGMS (grant no. GM089732) 2020-06-23T19:54:32Z 2020-06-23T19:54:32Z 2017-11-20 2017-09-17 2019-12-27T19:05:10Z Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 https://hdl.handle.net/1721.1/125956 Lindovska, Petra, and Mohammad Movassaghi, "Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines." Journal of the American Chemical Society 139, 48 (Nov. 2017): p. 17590-96 doi 10.1021/jacs.7b09929 ©2017 Author(s) en 10.1021/jacs.7b09929 Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Lindovska, Petra Movassaghi, Mohammad Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines |
| title | Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines |
| title_full | Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines |
| title_fullStr | Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines |
| title_full_unstemmed | Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines |
| title_short | Concise synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)-hodgkinsine b, (-)-quadrigemine c, and (-)-psycholeine via convergent and directed modular assembly of cyclotryptamines |
| title_sort | concise synthesis of hodgkinsine calycosidine hodgkinsine b quadrigemine c and psycholeine via convergent and directed modular assembly of cyclotryptamines |
| url | https://hdl.handle.net/1721.1/125956 |
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