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.