Highly Functionalized β‐Cyclodextrins by Solid‐Supported Synthesis

Abstract

Using covalent capture, a high yielding selective mono-functionalization of heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-β-CD with a 5-mercaptopentyl functional group has been achieved. Here, we demonstrate the immobilization of the mono-thiol functionalized β-CD on PEGA resin via a disulfide bond, enabling solid-phase elaboration of the remaining six primary amines. To showcase the potential of this method, the amines were elaborated to tripeptides through standard Fmoc-peptide chemistry. A small library of CD-tripeptide conjugates was generated which, when reduced from the solid support, could be tagged at the released thiol with an environmentally sensitive fluorophore. The resulting library of sensors showed potential for the differential sensing of various bile salts. The described methodology provides a rapid and versatile route to synthesize highly functionalized libraries of CD derivatives that may be tailored towards applications in sensing, catalysis, and multivalent displays.

Facile synthesis of a diverse library of mono-3-substituted β-cyclodextrin analogues

“…• Published procedures for isolating CD derivatives are typically complex, requiring chromatography, lyophilization, and/or centrifugation [35][36][37][38][39] . We wished to use the simpler purification approach of precipitation from DMF with acetone, but our initial attempts failed.…”

Facile Synthesis of a Diverse Library of Mono-3-substituted β-Cyclodextrin Analogues

“…• Published procedures for isolating CD derivatives are typically complex, requiring chromatography, lyophilization, and/or centrifugation [35][36][37][38][39] . We wished to use the simpler approach of purifying the modified CD products by precipitation from DMF with acetone, but our initial attempts failed because, although a visible precipitate formed on addition of acetone to the reaction vessel, the precipitate passed through the finest grades of filter paper.…”

Cyclodextrins-Peptides/Proteins Conjugates: Synthesis, Properties and Applications

“…Presumably, the observed response depended on the packing of the peptide side chains in the creation of a hydrophobic environment above the CD cavity. To conclude, the obtained conjugate of CD with peptide and fluorophore can be applied as a novel fluorescent sensor of bile salts; additionally, the CD can be conjugated with peptide on modified resin [ 127 ].…”