Asymmetric alpha-arylation of amino acids

Article

关键词: ENANTIOSELECTIVE SYNTHESIS;    SMILES REARRANGEMENT;    SELF-REGENERATION;    DERIVATIVES;    CHIRALITY;    MEMORY;    STEREOCENTERS;   

DOI  :  10.1038/s41586-018-0553-9

来源: SCIE

【 摘 要 】

Quaternary amino acids, in which the alpha-carbon that bears the amino and carboxyl groups also carries two carbon substituents, have an important role as modifiers of peptide conformation and bioactivity and as precursors of medicinally important compounds(1,2). In contrast to enantioselective alkylation at this alpha-carbon, for which there are several methods(3-8), general enantioselective introduction of an aryl substituent at the alpha-carbon is synthetically challenging(9). Nonetheless, the resultant alpha-aryl amino acids and their derivatives are valuable precursors to bioactive molecules(10,11). Here we describe the synthesis of quaternary alpha-aryl amino acids from enantiopure amino acid precursors by alpha-arylation without loss of stereochemical integrity. Our approach relies on the temporary formation of a second stereogenic centre in an N'-arylurea adduct(12) of an imidazolidinone derivative(6) of the precursor amino acid, and uses readily available enantiopure amino acids both as a precursor and as a source of asymmetry. It avoids the use of valuable transition metals, and enables arylation with electron-rich, electron-poor and heterocyclic substituents. Either enantiomer of the product can be formed from a single amino acid precursor. The method is practical and scalable, and provides the opportunity to produce alpha-arylated quaternary amino acids in multi-gram quantities.

【 授权许可】

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