Covalent [2]Catenane and [2]Rotaxane Synthesis via a δ-Amino Acid Template

Area of Science:

• Supramolecular Chemistry
• Organic Synthesis
• Chemical Biology

Background:

• Mechanically interlocked molecules (MIMs) are complex structures with unique mechanical bonds.
• Existing synthesis methods for MIMs often lack general applicability, especially for natural products like lasso peptides.
• Previous approaches often dictated structural components by the supramolecular preorganization method.

Purpose of the Study:

• To develop a generally applicable synthetic strategy for peptide-based MIMs.
• To utilize a novel covalent templating unit for MIM synthesis.
• To demonstrate the versatility of the approach for creating different interlocked architectures.

Main Methods:

• Employed an ester-functionalized, aromatic δ-amino acid as a central covalent templating unit.
• Synthesized a common multimacrocyclic intermediate.
• Utilized this intermediate to construct both a [2]catenane and a [2]rotaxane.

Main Results:

• Successfully synthesized a [2]catenane and a [2]rotaxane from a single intermediate.
• Demonstrated the utility of the δ-amino acid as an effective covalent template.
• Established a key step towards the synthesis of peptide-based interlocked products.

Conclusions:

• The developed method offers a versatile platform for synthesizing diverse MIMs.
• This work represents a significant advancement in the field of supramolecular chemistry and peptide synthesis.
• The approach is a crucial step towards the future construction of complex interlocked natural products.