Synthesis of cyclodextrin dimers via Diels–Alder reaction

Abstract

Cyclodextrins have been utilized as molecular capsules in pharmaceutical application. Cyclodextrin dimers exhibited the property of including larger compounds than cyclodextrin monomers. The fabrication of cyclodextrin dimers is challenging as it involves complicated synthesis and purification techniques. In this study, cyclodextrin dimers were synthesized via a facile procedure using the Diels–Alder reaction to construct a linker between two cyclodextrin units. Furan-substituted γ-CD and maleimide-substituted α-CD and γ-CD were efficiently synthesized in high yields. The furan- and maleimide-substituted cyclodextrins combined to form the desired dimers in water at 25 °C. The dimers disassembled at 75 °C via the retro-Diels–Alder reaction yielding furan and maleimide cyclodextrin monomers, confirmed using ¹H NMR spectroscopy. The γ-CD-γ-CD dimer exhibited a high binding constant for tropaeolin OO due to having a wider and more suitable cavity than the monomers. The Diels–Alder reaction can be an efficient strategy for constructing cyclodextrin dimers possessing inclusion abilities.

Graphical Abstract

Keywords:

• Cyclodextrin
• Diels–Alder reaction
• dimerization
• inclusion complex

Declaration of interest statement

The authors report there are no competing interests to declare.