Controlling Helix Sense at N- and C-Termini in Quinoline Oligoamide Foldamers by β-Pinene-Derived Pyridyl Moieties

Abstract

A series of quinoline oligoamide foldamers bearing a β-pinene-derived pyridyl group at the N-terminus or the C-terminus were synthesized, and the efficiencies of chiral inductions have been evaluated by H NMR and CD spectra. The chiral inductions were quantitative when chiral pyridyl acid was appended at the N-terminus, but were inferior when chiral pyridyl amine was appended at the C-terminus. Unexpectedly, N-oxidation on the pyridine ring at the C-terminus does not notably enhance the chiral induction efficiency in spite of the presence of three-center hydrogen bonds.

Chiral Induction and Remote Chiral Communication in Quinoline Oligoamide Foldamers for Determination of Enantiomeric Excess and Absolute Configuration of Chiral Amines and Their Derivatives

“…Interestingly, the 1 H NMR spectra of Q5C‐ S and Q5N‐ S ( Q5‐MA1‐ S ) exhibit completely different split patterns of the protons in amides (Figure a and d), demonstrating that the same chiral group exerts different chiral inductions at the C‐ and N‐termini of the quinoline oligoamide foldamer, respectively. The CD spectra showed that MA1‐ S induces a P helix when connected at the C‐terminus of Q5 but M helix when connected at the N‐terminus (Figure a and d), which is different from the previous observations that the same chiral center induced the same handedness at the two termini of a foldamer …”

“…A positive or negative Cotton effect with a maximum amplitude at 385 nm was observed, respectively, when Q5 was treated with MA1‐ R or MA1‐ S . The CD spectra of the resulting chiral foldamers feature bands in the absorption region of quinoline rings between 250 and 500 nm, consistent with our previous observations . The generation of strong CD signals revealed that the central chirality of MA1‐ R / S was successfully amplified and transferred into the helical chirality of the quinoline foldamers (Figure a) and ruled out potential interference with chiral impurities that might be present in an unknown sample.…”

“…Encouraged by the above result, the pro‐activated pentameric foldamer Q5 , containing the fluoroarene motif was designed and synthesized (Scheme b and S1). Previous investigations have shown that the pentamer of quinoline oligoamide foldamer is long enough to undergo slow helix handedness interconversion on the NMR timescale in CDCl 3 at 298 K . The N‐nucleophilic substitution reaction of Q5 with chiral amine MA1‐ R was performed under the conditions detailed above.…”

Supramolecular Assemblies Based on Intramolecular Three-Center Hydrogen Bond and their Applications

“…在此基础上, 江华等 [55][56][57] 将手性基团引入低聚喹啉 酰胺折叠体的 N-端或 C-端, 可以诱导其形成手性螺旋 体. 例如, 江华等 [55] 将手性 β-蒎烯衍生吡啶酸引入寡聚 喹啉酰胺折叠体的 N-端, 合成得到手性螺旋低聚物 34.…”

Distance‐Dependent Chiral Communication between Two Quinoline Oligoamide Foldamers Connected by Alkyl Chains

“…[8] Quinoline oligoamide foldamer (QOF) is considered to be an excellent scaffold to investigate chiral induction because of its efficient synthetic procedure, stable helical structure and high-fidelity for chiral transfer. [9] Huc [10] and our group [11] have reported several chiral moieties that can bias one helical preference even absolute one-handed helicity, but examples on the chiral communication between two foldamers connected by linkers is still underexplored. [7a-c,e] Previously, Huc reported that the chiral communication is highly efficient when two helically folded oligomers was connected at end to end by flexible linkers but is completely interrupted when connected by semi-rigid linkers.…”