Jump to main content
Jump to site search

Issue 4, 2015
Previous Article Next Article

Enantioselective synthesis of D-α-amino amides from aliphatic aldehydes

Author affiliations


Peptides consisting of D-amino amides are highly represented among both biologically active natural products and non-natural small molecules used in therapeutic development. Chemical synthesis of D-amino amides most often involves approaches based on enzymatic resolution or fractional recrystallization of their diastereomeric amino acid salt precursors, techniques that produce an equal amount of the L-amino acid. Enantioselective synthesis, however, promises selective and general access to a specific α-amino amide, and may enable efficient peptide synthesis regardless of the availability of the corresponding α-amino acid. This report describes the use of a cinchona alkaloid-catalyzed aza-Henry reaction using bromonitromethane, and the integration of its product with umpolung amide synthesis. The result is a straightforward 3-step protocol beginning from aliphatic aldehydes that provides homologated peptides bearing an aliphatic side chain at the resulting D-α-amino amide.

Graphical abstract: Enantioselective synthesis of d-α-amino amides from aliphatic aldehydes

Back to tab navigation

Supplementary files

Publication details

The article was received on 07 Jan 2015, accepted on 16 Feb 2015 and first published on 27 Feb 2015

Article type: Edge Article
DOI: 10.1039/C5SC00064E
Citation: Chem. Sci., 2015,6, 2590-2595
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Enantioselective synthesis of D-α-amino amides from aliphatic aldehydes

    K. E. Schwieter and J. N. Johnston, Chem. Sci., 2015, 6, 2590
    DOI: 10.1039/C5SC00064E

Search articles by author