Asymmetric synthesis of d-fagomine and its diastereoisomers
A divergent strategy for the asymmetric syntheses of d-fagomine and three of its diastereoisomers has been developed. The diastereoselective conjugate addition of an enantiopure lithium amide to an α,β-unsaturated ester was used as the key step to install the correct configuration required for the C...
| Κύριοι συγγραφείς: | , , , , |
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| Μορφή: | Journal article |
| Έκδοση: |
Elsevier
2018
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| _version_ | 1826300058558005248 |
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| author | Davies, S Fletcher, A Kennedy, M Roberts, P Thomson, J |
| author_facet | Davies, S Fletcher, A Kennedy, M Roberts, P Thomson, J |
| author_sort | Davies, S |
| collection | OXFORD |
| description | A divergent strategy for the asymmetric syntheses of d-fagomine and three of its diastereoisomers has been developed. The diastereoselective conjugate addition of an enantiopure lithium amide to an α,β-unsaturated ester was used as the key step to install the correct configuration required for the C(5)-stereogenic centre within the targets. In situ enolate oxidation generated the corresponding anti-α-hydroxy-β-amino ester, which possessed the correct configuration required for the C(4)-stereogenic centre within both d-fagomine and d-3-epi-fagomine. Subsequent epimerisation of this key anti-α-hydroxy-β-amino ester upon oxidation and diastereoselective reduction gave the corresponding syn-α-hydroxy-β-amino ester, which possessed the correct configuration required for the C(4)-stereogenic centre within both d-4-epi-fagomine and d-5-epi-fagomine. Elaboration of both α-hydroxy-β-amino esters upon reduction to the corresponding aldehydes followed by aldol reaction generated the requisite C(3)-stereogenic centres within the target compounds, then cyclisation and deprotection gave the enantiopure iminosugars in good overall yields, as single diastereoisomers (>99:1 dr). |
| first_indexed | 2024-03-07T05:11:22Z |
| format | Journal article |
| id | oxford-uuid:dba842c0-ad5c-4348-b96b-9a8dc8e8b855 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:11:22Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:dba842c0-ad5c-4348-b96b-9a8dc8e8b8552022-03-27T09:12:12ZAsymmetric synthesis of d-fagomine and its diastereoisomersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dba842c0-ad5c-4348-b96b-9a8dc8e8b855Symplectic Elements at OxfordElsevier2018Davies, SFletcher, AKennedy, MRoberts, PThomson, JA divergent strategy for the asymmetric syntheses of d-fagomine and three of its diastereoisomers has been developed. The diastereoselective conjugate addition of an enantiopure lithium amide to an α,β-unsaturated ester was used as the key step to install the correct configuration required for the C(5)-stereogenic centre within the targets. In situ enolate oxidation generated the corresponding anti-α-hydroxy-β-amino ester, which possessed the correct configuration required for the C(4)-stereogenic centre within both d-fagomine and d-3-epi-fagomine. Subsequent epimerisation of this key anti-α-hydroxy-β-amino ester upon oxidation and diastereoselective reduction gave the corresponding syn-α-hydroxy-β-amino ester, which possessed the correct configuration required for the C(4)-stereogenic centre within both d-4-epi-fagomine and d-5-epi-fagomine. Elaboration of both α-hydroxy-β-amino esters upon reduction to the corresponding aldehydes followed by aldol reaction generated the requisite C(3)-stereogenic centres within the target compounds, then cyclisation and deprotection gave the enantiopure iminosugars in good overall yields, as single diastereoisomers (>99:1 dr). |
| spellingShingle | Davies, S Fletcher, A Kennedy, M Roberts, P Thomson, J Asymmetric synthesis of d-fagomine and its diastereoisomers |
| title | Asymmetric synthesis of d-fagomine and its diastereoisomers |
| title_full | Asymmetric synthesis of d-fagomine and its diastereoisomers |
| title_fullStr | Asymmetric synthesis of d-fagomine and its diastereoisomers |
| title_full_unstemmed | Asymmetric synthesis of d-fagomine and its diastereoisomers |
| title_short | Asymmetric synthesis of d-fagomine and its diastereoisomers |
| title_sort | asymmetric synthesis of d fagomine and its diastereoisomers |
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