Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds
A series of highly substituted tetrahydrofurans (THFs), decorated with modifiable 2‐aryl, 3‐carboxy and 4‐amino substituents, has been prepared for biological evaluation within the European Lead Factory. Diastereoselective reductive amination of pre‐functionalised 4‐oxofurans, readily prepared from...
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Wiley
2018
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| Online Access: | https://eprints.nottingham.ac.uk/51685/ |
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| author | Moody, Christopher J. Wales, Steven M. Merisor, Elena Adcock, Holly Pearce, Christopher A. Strutt, Ian Lewis, William Hamza, Daniel |
| author_facet | Moody, Christopher J. Wales, Steven M. Merisor, Elena Adcock, Holly Pearce, Christopher A. Strutt, Ian Lewis, William Hamza, Daniel |
| author_sort | Moody, Christopher J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | A series of highly substituted tetrahydrofurans (THFs), decorated with modifiable 2‐aryl, 3‐carboxy and 4‐amino substituents, has been prepared for biological evaluation within the European Lead Factory. Diastereoselective reductive amination of pre‐functionalised 4‐oxofurans, readily prepared from cinnamate esters via oxa Michael/Dieckmann annulation, provided the requisite THF cores on gram scale with three contiguous stereocentres, including full substitution at C‐3. In a second series, a pyrrolidine ring was fused to the same oxofuran scaffold via an intramolecular reductive amination, inverting the configuration at C‐4 relative to the other ring substituents. The resulting compounds, which displayed desirable physical properties as lead‐like scaffolds, were derivatised into a small library of 24 compounds, demonstrating their ability to serve as starting points for drug discovery. Ultimately, this chemistry enabled the preparation of 1948 THF‐containing compounds for inclusion in the Joint European Compound Library. |
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| id | nottingham-51685 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:21:34Z |
| publishDate | 2018 |
| publisher | Wiley |
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| repository_type | Digital Repository |
| spelling | nottingham-516852019-04-14T04:30:12Z https://eprints.nottingham.ac.uk/51685/ Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds Moody, Christopher J. Wales, Steven M. Merisor, Elena Adcock, Holly Pearce, Christopher A. Strutt, Ian Lewis, William Hamza, Daniel A series of highly substituted tetrahydrofurans (THFs), decorated with modifiable 2‐aryl, 3‐carboxy and 4‐amino substituents, has been prepared for biological evaluation within the European Lead Factory. Diastereoselective reductive amination of pre‐functionalised 4‐oxofurans, readily prepared from cinnamate esters via oxa Michael/Dieckmann annulation, provided the requisite THF cores on gram scale with three contiguous stereocentres, including full substitution at C‐3. In a second series, a pyrrolidine ring was fused to the same oxofuran scaffold via an intramolecular reductive amination, inverting the configuration at C‐4 relative to the other ring substituents. The resulting compounds, which displayed desirable physical properties as lead‐like scaffolds, were derivatised into a small library of 24 compounds, demonstrating their ability to serve as starting points for drug discovery. Ultimately, this chemistry enabled the preparation of 1948 THF‐containing compounds for inclusion in the Joint European Compound Library. Wiley 2018-07-07 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/51685/1/Chris%20Moody%20Diastereoselective%20Synthesis.pdf Moody, Christopher J., Wales, Steven M., Merisor, Elena, Adcock, Holly, Pearce, Christopher A., Strutt, Ian, Lewis, William and Hamza, Daniel (2018) Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds. Chemistry - A European Journal, 24 (32). pp. 8233-8239. ISSN 1521-3765 tetrahydrofurans; pyrrolidines; heterocycles; drug discovery; lead-oriented synthesis https://onlinelibrary.wiley.com/doi/10.1002/chem.201801046 doi:10.1002/chem.201801046 doi:10.1002/chem.201801046 |
| spellingShingle | tetrahydrofurans; pyrrolidines; heterocycles; drug discovery; lead-oriented synthesis Moody, Christopher J. Wales, Steven M. Merisor, Elena Adcock, Holly Pearce, Christopher A. Strutt, Ian Lewis, William Hamza, Daniel Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds |
| title | Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds |
| title_full | Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds |
| title_fullStr | Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds |
| title_full_unstemmed | Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds |
| title_short | Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds |
| title_sort | diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds |
| topic | tetrahydrofurans; pyrrolidines; heterocycles; drug discovery; lead-oriented synthesis |
| url | https://eprints.nottingham.ac.uk/51685/ https://eprints.nottingham.ac.uk/51685/ https://eprints.nottingham.ac.uk/51685/ |