Foldamer-mediated remote stereocontrol: >1,60 asymmetric induction

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Polymer Science

Background:

• Peptide foldamers offer tunable structures for various applications.
• Controlling the helical screw sense in foldamers is crucial for predictable function.
• Achiral building blocks typically result in random helical structures.

Purpose of the Study:

• To investigate the effect of N-terminal chiral residues on achiral foldamer helicity.
• To demonstrate the transfer of stereochemical information along the foldamer backbone.
• To achieve diastereoselective reactions using controlled foldamer conformation.

Main Methods:

• Synthesis of foldamers from achiral amino acids (Aib, Ac6c).
• Incorporation of an N-terminal L-α-methylvaline dimer.
• Analysis of helical conformation and screw sense.
• Performing diastereoselective reactions (alkene hydrogenation, iminium ion addition).

Main Results:

• Complete conformational control over helix screw sense was achieved.
• A persistent right-handed helix preference was observed.
• Diastereoselective reactions showed induction up to 1,61 positions.
• Stereochemical information was communicated over distances up to 4 nm.

Conclusions:

• N-terminal chiral dimers can dictate foldamer helicity.
• This control enables long-range stereochemical communication.
• Foldamers can be engineered for precise diastereoselective synthesis.