title: 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 amine salts, 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.
authors.affiliation: Department of Chemistry and Vanderbilt Institute of Chemical Biology Vanderbilt University, Nashville, Tennessee 37235.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Schwieter
authors.affiliation: Department of Chemistry and Vanderbilt Institute of Chemical Biology Vanderbilt University, Nashville, Tennessee 37235.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Johnston
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