Trading N and O. Part 4: Asymmetric synthesis of syn-β-substituted-α-amino acids

TETRAHEDRON

卷:74

Article

Davies, Stephen G.¹  Fletcher, Ai M.¹  Greenaway, Catherine J.¹  Kennedy, Matthew S.¹  Mayer, Christoph¹  Roberts, Paul M.¹  Thomson, James E.¹ 

[1] Univ Oxford, Dept Chem, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England

关键词: beta-Substituted-alpha-amino acid;    beta-Hydroxy-alpha-amino acid;    beta-Fluoro-alpha-amino acid;    Aziridinium ion;    Lithium amide;    Asymmetric synthesis;   

DOI  :  10.1016/j.tet.2018.04.071

来源: Elsevier

【 摘 要 】

A total of nine enantiopure syn-beta-substituted-alpha-amino acids have been synthesised, comprising both syn-beta-hydroxy-alpha-amino acids and syn-beta-fluoro-alpha-amino acids. The key step in the synthetic strategy towards these syn-beta-substituted-alpha-amino acids involves a stereospecific rearrangement, which proceeds via the intermediacy of the corresponding aziridinium ions. The requisite enantiopure syn-alpha-hydroxy-beta-amino esters were prepared via asymmetric aminohydroxylation of the corresponding alpha,beta-unsaturated esters followed by epimerisation of the resultant anti-alpha-hydroxy-beta-amino esters at the C(2)-position. Subsequent activation of the alpha-hydroxy moiety as a leaving group followed by displacement by the beta-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-beta-hydroxy-alpha-amino ester or syn-beta-fluoro-alpha-amino ester, respectively, and N-deprotection and ester hydrolysis afforded the target syn-beta-substituted-alpha-amino acids as single diastereoisomers in good overall yield. (C) 2018 Published by Elsevier Ltd.

【 授权许可】

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