Issue 4, 2015

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

Abstract

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

Supplementary files

Article information

Article type
Edge Article
Submitted
07 Jan 2015
Accepted
16 Feb 2015
First published
27 Feb 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2015,6, 2590-2595

Author version available

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

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