Trading N and O. Part 4: Asymmetric synthesis of syn-β-substituted-α-amino acids
| Autor: | Catherine J. Greenaway, James E. Thomson, Matthew S. Kennedy, Stephen G. Davies, Christoph Mayer, Ai M. Fletcher, Paul M. Roberts |
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| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Stereochemistry Organic Chemistry Substituent Enantioselective synthesis Diastereomer Leaving group Regioselectivity 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences Amino acid chemistry.chemical_compound Enantiopure drug chemistry Drug Discovery Moiety heterocyclic compounds |
| Zdroj: | Tetrahedron. 74(38) |
| ISSN: | 1464-5416 0040-4020 |
| Popis: | A total of nine enantiopure syn-β-substituted-α-amino acids have been synthesised, comprising both syn-β-hydroxy-α-amino acids and syn-β-fluoro-α-amino acids. The key step in the synthetic strategy towards these syn-β-substituted-α-amino acids involves a stereospecific rearrangement, which proceeds via the intermediacy of the corresponding aziridinium ions. The requisite enantiopure syn-α-hydroxy-β-amino esters were prepared via asymmetric aminohydroxylation of the corresponding α,β-unsaturated esters followed by epimerisation of the resultant anti-α-hydroxy-β-amino esters at the C(2)-position. Subsequent activation of the α-hydroxy moiety as a leaving group followed by displacement by the β-amino substituent gave the corresponding aziridinium species. Regioselective in situ ring-opening of the aziridinium intermediates with either water or fluoride gave the corresponding syn-β-hydroxy-α-amino ester or syn-β-fluoro-α-amino ester, respectively, and N-deprotection and ester hydrolysis afforded the target syn-β-substituted-α-amino acids as single diastereoisomers in good overall yield. |
| Databáze: | OpenAIRE |
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