Introduction to Unnatural Foldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 64

H

H R N H

R γ NH

CH 2

C γ

H

θ 1 θ 2 ψ

R H

φ

H 2 C θ 1 θ 2 ψ

H

γ α

N

C α

H

H

β φ H O

H H O

H O

O

C β

n O

4 -peptide
(2.6 helix)

γ

θ 1 = +70° θ 2 = +60° ψ = -140° Σ = -130°

φ = -120°

H R N H

H NH

H

NH NH H

R γ

R

H

θ 1 θ 2

φ ψ

H 2 C θ 1 ' ψ '

RHC

H

N

HN H

φ H O θ 2

N

H

O

H

O CH 2

H O

O

n

N,N'-oligourea
(2.5 helix)

φ = -100° θ 1 = +55° θ 2 = +85° ψ = -130°

Σ = -130°

Figure 2.16 Comparison of main chain dihedral angles between helical N,N 0 -linked oli-
gourea and g 4 -peptide backbones.

14-helical fold [59]. g-Amino acid residues within the 14-helix are characterized by large
c values 140 ) [60]. The additional nitrogen was believed to act as a rigidi-

fying element by fixing the pseudo c angle to a value close to 170-180 . Detailed NMR
studies provided compelling evidence that enantiopure N , N 0 -linked oligoureas adopt a
well defined and stable 2.5-helical fold, akin to the g

140 (or

4 -peptide 14-helix [61]. The helix
is right-handed with a pitch of about 5.1 A and held by H-bonds closing both 12- and
14-membered rings (12/14-helix). The structural analogy between oligourea and the
g-peptide helical backbone is evident when comparing the main backbone torsion angles
(Figure 2.16).

2.2.6 Foldamers of a -Aminoxy Acids

a-Aminoxy acids are analogues of b-amino acids in which the b-carbon atom in the
b-amino acid backbone is replaced by an oxygen atom [62]. The first synthesis of an
a-aminoxy diamide was reported by Yang's group in 1996 [63]. Theoretical calculations
suggest that it adopts a rigid eight-membered ring hydrogen-bonded structure (so-called
a N-O turn) in its most favorable conformation (Figure 2.17). In the presence of side
chains, ab initio calculation results suggest that chiral L -a-aminoxy acids prefer a left-
handed chiral N - O turn.
The formation of a rigid a N - O turn structure in a-aminoxy diamides suggested that
oligomers of aminoxy acids might have interesting conformational features and prompted
their investigation. Thus, a series of oligomers was synthesized and subjected to confor-
mational studies as performed previously for a-aminoxy diamides (the longest one is

PhH 2 CO

O

OCH 3

CH 3 NH

O

O H N O H N

O H N

O

HN HN HN

O O O

O O O

Figure 2.17 Some examples of dipeptides containing a-aminoxy acids (the a N - O turn is
shown).