Helical Foldamers From Aromatic Ether Based Amino Acid Oligomers:Synthesis,Structure And Induction Of Single-Handed Helicity

Artificial construction of helical structures to mimic biomolecules is a hot topic in supramolecular chemistry,both from natural or unnatural building blocks.Because of its high strength(as high as 120 k J/mol)and high directionality,hydrogen bonding is the interaction of first choice for this mission.The thesis aimed at construction of helical foldamers via intramolecular hydrogen bonding interaction from a completely new building block——aromatic ether based amino acid.The oligomers with varied lengths were synthesized via multiple iterative steps of organic synthesis.Firstly,starting from cheap and readily available materials——methyl salicylate and o-fluoronitrobenzene,the aromatic ether building block with nitro and ester groups was synthesized with high efficiency via aromatic nucleophilic substitution reaction(S_NAr).Subsequent catalytic hydrogenation reduction of nitro to amino and hydrolysis of ester,we got the basic building block——aromatic ether based amino acid,for helical foldamers.For the synthesis of aromatic ether amino acid based oligomers Helix-2?Helix-10,and Helix-2R?Helix-10R/Helix-4S with chiral auxiliary groups,a one-way growth,stepwise iterative synthetic route was adapted,mainly through catalytic hydrogenation reduction of nitro to amino and coupling of acyl chloride&amino to form an amide.The primary chemical structures were determined via NMR and MS.Based on the preliminary results of solubility tests and~1H NMR studies,the oligomers might adopted regular helical conformation in solution via synergistic interaction of the turn structure in aromatic ether bond and the intramolecular bifurcated hydrogen bonds.CD investigations on Helix-2R?Helix-10R/Helix-4S indicated formation of single handed helical structures due to the chiral auxiliary groups.X-ray single crystal analysis further confirmed that there are left-handed and right-handed conformations for achiral series.However,only one conformation is observed for chiral series with chiral auxiliary group.In summary,the study of the current thesis provided a new model of helical structure,which would enhance our understanding on the helical structures of biomolecules.