A Direct One-Pot Modification of β-Cyclodextrin via the Ugi-Five-Component Reaction

Starch-derived beta-cyclodextrins (beta-CDs) are used in pharmacy or the food and cosmetic industry as drug deliverers, separating agents, catalysts, detergents, or viscosity modifiers. However, solubility issues often restrict their potential applications. Here, we report a straightforward and direct one-pot synthesis for the modification of beta-CDs based on the Ugi-five-component reaction (Ugi-5CR). The Ugi-5CR requires to react an amine, an aldehyde, an isocyanide, carbon dioxide and the beta-CD, which serves as alcohol component. Overall, five modified beta-CDs containing carbamate moieties were synthesized at room temperature in a high pressure reactor (10 bar) within 24 hours. The successful modifications are verified by mass spectrometry, nuclear magnetic resonance, and infrared spectroscopy, indicating one to three reacted primary hydroxyl groups per beta-CD. Additionally, we report altered solubility behavior of two of the five modified beta-CDs.