Synthesis and conformational analysis are reported for molecules containing the
trans-5-amino-3,4-dimethylpent-3-enoic acid residue (ADPA,
1). This amino acid is a glycylglycine mimic, in which thecentral amide group is replaced with an
E-tetrasubstituted alkene. It was anticipated that this isosteric replacementwould promote specific local (
-turn) and nonlocal (
-hairpin) conformational preferences. Previous work hasshown that the most common
-turn conformations (type I and type II) are not strong inducers of
-hairpinformation, while the rare "mirror image"
-turns (type I' and type II') promote
-hairpin formation. We thereforesought an achiral unit with a strong turn-forming propensity, since the lack of stereogenic centers within sucha unit would eliminate the energetic distinction between common and "mirror image" turn conformations. In,the ADPA unit, avoidance of allylic strain was expected to preorganize the backbone for adoption of foldedconformations. A combination of NMR and IR data for di-, tri-, and tetrapeptide analogues containing theADPA residue reveal that
-turn- and
-hairpin-like folding is promoted in methylene chloride solution.
