Predictable Conformational Diversity in Foldamers of Sugar Amino Acids.

A systematic conformational search was carried out for monomers and homohexamers of furanoid β-amino acids: cis-(S,R) and trans-(S,S) stereoisomers of aminocyclopentane carboxylic acid (ACPC), two different aminofuranuronic acids (AFUα and AFUβ), their isopropylidene derivatives (AFU(ip)), and the key intermediate β-aminotetrahydrofurancarboxylic acid (ATFC). The stereochemistry of the building blocks was chosen to match that of the natural sugar amino acid (xylose and ribose) precursors (XylAFU and RibAFU). The results show that hexamers of cis-furanoid β-amino acids show great variability: while hydrophobic cyclopentane (cis-ACPC)6 and hydrophilic (XylAFUα/β)6 foldamers favor two different zigzagged conformation as hexamers, the backbone fold turns into a helix in the case of (cis-ATFC)6 (10-helix) and (XylAFU(ip))6 (14-helix). Trans stereochemistry resulted in hexamers exclusively with the right-handed helix conformation, (H12P)6, regardless of their polarity. We found that the preferred oligomeric structure of XylAFUα/β is conformationally compatible with β-pleated sheets, while that of the trans/(S,S) units matches with α-helices of proteins.