Skip to content

Asymmetric α-Arylation of Amino Acids

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)105-109
Number of pages5
JournalNature
Volume562
Issue number7725
Early online date4 Oct 2018
DOIs
DateAccepted/In press - 17 Aug 2018
DateE-pub ahead of print - 4 Oct 2018
DatePublished (current) - Oct 2018

Abstract

Quaternary amino acids, in which the α-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 compounds1,2. In contrast to enantioselective alkylation at this α-carbon, for which there are several methods3,4,5,6,7,8, general enantioselective introduction of an aryl substituent at the α-carbon is synthetically challenging9. Nonetheless, the resultant α-aryl amino acids and their derivatives are valuable precursors to bioactive molecules10,11. Here we describe the synthesis of quaternary α-aryl amino acids from enantiopure amino acid precursors by α-arylation without loss of stereochemical integrity. Our approach relies on the temporary formation of a second stereogenic centre in an N′-arylurea adduct12 of an imidazolidinone derivative6 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 α-arylated quaternary amino acids in multi-gram quantities.

Download statistics

No data available

Documents

Documents

  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Nature at https://www.nature.com/articles/s41586-018-0553-9 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 953 KB, PDF document

DOI

View research connections

Related faculties, schools or groups