Solid Phase Synthesis of Helically Folded Aromatic Oligoamides.

Area of Science:

• Organic Chemistry
• Polymer Chemistry
• Biomimetic Chemistry

Background:

• Aromatic amide foldamers are oligomers with stable, predictable folded structures.
• They serve as synthetic mimics for proteins.
• Oligomers of amino quinoline carboxylic acids form well-defined helices.

Purpose of the Study:

• To develop and optimize solid phase synthesis (SPS) protocols for aromatic amide foldamers.
• To overcome synthetic challenges associated with these backbones, such as low nucleophilicity and folding on solid phase.
• To enable rapid production of diverse foldamer sequences.

Main Methods:

• Detailed SPS protocols were developed for specific foldamer types.
• Protocols address challenges using methods like acid chloride activation and microwave assistance.
• Synthesis of oligomers of 8-amino-2-quinolinecarboxylic acid, fluorinated analogs, and heteromeric sequences with alpha-amino acids were achieved.

Main Results:

• Efficient SPS protocols were established for producing various aromatic amide foldamers.
• These methods facilitate rapid synthesis without intermediate purification.
• An octamer sequence was synthesized and purified within one to two weeks.

Conclusions:

• Optimized SPS protocols provide a rapid and efficient route to aromatic amide foldamers.
• These synthetic advancements accelerate the design and development of protein mimics.
• The developed methods allow for diverse sequence construction with varied components.