Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids
The β-hydroxy-α-amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-amino esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2014
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| _version_ | 1797098592576471040 |
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| author | Davies, S Fletcher, A Frost, AB Roberts, P Thomson, J |
| author_facet | Davies, S Fletcher, A Frost, AB Roberts, P Thomson, J |
| author_sort | Davies, S |
| collection | OXFORD |
| description | The β-hydroxy-α-amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-amino esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding aziridinium ions. The starting anti-α-hydroxy-β-amino esters were prepared in >99:1 dr using our diastereoselective aminohydroxylation procedure, whereby conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester is followed by oxidation of the resultant enolate with (-)-camphorsulfonyloxaziridine. Subsequent activation of the hydroxyl group within the anti-α-hydroxy-β-amino esters promoted aziridinium ion formation [which proceeds with inversion of configuration at C(2)], and regioselective ring-opening of the intermediate aziridinium ions with H2O [which proceeds with inversion of configuration at C(3)] gave the corresponding anti-β-hydroxy-α-amino esters as single diastereoisomers (>99:1 dr). Deprotection of these substrates via sequential hydrogenolysis and ester hydrolysis gave the corresponding β-hydroxy-α-amino acids in good yield and high diastereoisomeric and enantiomeric purity. |
| first_indexed | 2024-03-07T05:11:49Z |
| format | Journal article |
| id | oxford-uuid:dbd0274d-f81c-4d13-8daa-6eb0d709d33c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:11:49Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:dbd0274d-f81c-4d13-8daa-6eb0d709d33c2022-03-27T09:13:18ZTrading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acidsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dbd0274d-f81c-4d13-8daa-6eb0d709d33cEnglishSymplectic Elements at OxfordElsevier2014Davies, SFletcher, AFrost, ABRoberts, PThomson, JThe β-hydroxy-α-amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-amino esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding aziridinium ions. The starting anti-α-hydroxy-β-amino esters were prepared in >99:1 dr using our diastereoselective aminohydroxylation procedure, whereby conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester is followed by oxidation of the resultant enolate with (-)-camphorsulfonyloxaziridine. Subsequent activation of the hydroxyl group within the anti-α-hydroxy-β-amino esters promoted aziridinium ion formation [which proceeds with inversion of configuration at C(2)], and regioselective ring-opening of the intermediate aziridinium ions with H2O [which proceeds with inversion of configuration at C(3)] gave the corresponding anti-β-hydroxy-α-amino esters as single diastereoisomers (>99:1 dr). Deprotection of these substrates via sequential hydrogenolysis and ester hydrolysis gave the corresponding β-hydroxy-α-amino acids in good yield and high diastereoisomeric and enantiomeric purity. |
| spellingShingle | Davies, S Fletcher, A Frost, AB Roberts, P Thomson, J Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids |
| title | Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids |
| title_full | Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids |
| title_fullStr | Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids |
| title_full_unstemmed | Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids |
| title_short | Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids |
| title_sort | trading n and o part 2 exploiting aziridinium intermediates for the synthesis of β hydroxy α amino acids |
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