Access to Versatile β-Cyclodextrin Scaffolds through Guest-Mediated Monoacylation.

Area of Science:

• Carbohydrate Chemistry
• Supramolecular Chemistry
• Organic Synthesis

Background:

• Cyclodextrins (CDs) are versatile cyclic oligosaccharides with a hydrophobic cavity and hydrophilic exterior.
• Selective functionalization of CDs is crucial for developing advanced materials and applications.
• Existing methods for CD derivatization often lack specificity and efficiency.

Purpose of the Study:

• To develop a novel strategy for the selective mono-derivatization of heptakis[6-deoxy-6-(2-aminoethylsulfanyl)]-β-CD.
• To introduce an amine-orthogonal thiol group onto the primary rim of β-CD for further modifications.
• To demonstrate the utility of this method for synthesizing heterofunctionalized β-CD constructs.

Main Methods:

• A guest-mediated covalent capture strategy was employed.
• Guests functionalized with cleavable linkers were used to guide the derivatization.
• Selective installation of a thiol group on the primary rim of β-CD was achieved.

Main Results:

• Two novel monoacylated β-CDs were synthesized with high yield and purity.
• The introduced thiol group served as a versatile handle for further chemical transformations.
• Facile linker cleavage and subsequent modification at the thiol group were demonstrated.

Conclusions:

• The developed guest-mediated covalent capture strategy enables selective mono-derivatization of β-CDs.
• This methodology provides a robust platform for creating heterofunctionalized β-CDs.
• The synthesized β-CD constructs hold potential for applications in analyte sensing and drug delivery.