Stereospecific synthesis of conformationally constrained gamma-amino acids: new foldamer building blocks that support helical secondary structure.
A highly stereoselective synthesis of novel cyclically constrained gamma-amino acid residues is presented. The key step involves organocatalytic Michael addition of an aldehyde to 1-nitrocyclohexene. After aldehyde reduction, this approach provides optically active beta-substituted delta-nitro alcohols (96-99% ee), which can be converted to gamma-amino acid residues with a variety of substituents at the alpha position. We have used these new building blocks to prepare alpha/gamma-peptide foldamers that adopt a specific helical conformation in solution and in the solid state.
Guo
Li
L
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Chi
Yonggui
Y
Almeida
Aaron M
AM
Guzei
Ilia A
IA
Parker
Brian K
BK
Gellman
Samuel H
SH
D000447:Aldehydes / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis*; D008968:Molecular Conformation; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D000447:Aldehydes; D000596:Amino Acids