β ‑pinene
is an optically active and racemic molecule, which presents in
turpentine oils. It was demonstrated that when β‑pinene synergizes with
paclitaxel, they can suppress lung carcinoma cells. The geometrical
structure of β -pinene with chiral atom has big space steric
hindrance, which is benefit for the synthesis of chiral foldamers.
Therefore, a lot of study has been reported on enantio-selective ofβ ‑pinene derived molecular [7,8]. In 2017,
the study that β ‑pinene-derived pyridyl group can induce the
handedness of oligoamide foldamers has been reported[9]. Experimental data has shown thatβ -pinene-derived pyridyl connecting with quinoline oligoamide
behave better selection of handedness at N-terminal than at C-terminals.
They had investigated three types of foldamers, and thought that
hydrogen bond should be an obvious factors of helical handedness.
However, it is reported that hydrogen bonds, steric hindrance and
electrostatics are responsible for the helical handedness either in the
C-terminal or N-terminal in some works [10,11]. In
order to reveal the intrinsic reason for better selection of helix-sense
at N-terminal than at C-terminal, six experimental synthesized and two
designed oligoamide foldamers substituted by β -pinene have been
investigated in this paper. Six synthesized oligoamides include four
foldamers containing β -pinene-derived pyridyl amine at the
C-terminal (1a, 1b, 2a, and 2b) , two foldamers
containing β - pinene-derived pyridyl carboxylic acid at the
N-terminal (3a and 3b ). Two designed oligoamides include two
foldamers containing three-center hydrogen bonds at N-terminal
(4a and 4b ). Four types of foldamers (1-4 )
have been designed and they have been shown in Scheme 1. In
foldamer 1–4 , na represents R chirality ofβ -pinene, nb represents S chirality of β -pinene.
Because Zheng et al. have found that these foldamers are stable in
chloroform (CDCl3), CDCl3 was selected
as the solvent environment here. Based on the metadynamics simulations,
the helical handedness of four types of foldamers withβ ‑pinene-derived pyridine has been calculated. From the data of
the dihedral angle, rotation angle, and electronic orbitals
constitutions of foldamers, the key factors of chiral induction toβ ‑pinene substituted foldamers have been analyzed and discussed.
Scheme 1. The structures of the foldamer 1–4
2. Results and Discussion
To obtain P or M helical bias of foldamers in the solvent, all
investigated foldamers were put into a chloroform box. The metadynamics
method was applied to investigate helical inversion of pentameric1–4 in chloroform, and force field parameters specifically
were optimized for the arylamides containing quinoline-based.
Computations were systematically performed on each enantiomer to assess
their reproducibility.
2.1. Helix handedness of oligomers (1a/1b) substituted byβ -pinene-derived pyridyl amine at C-terminal