A New Access to Homo- and Heterodimers of α-, β-, and γ-Cyclodextrin by a Microwave-Promoted Huisgen Cycloaddition

A new and efficient synthetic protocol for the preparation of alpha-, beta- and gamma-cyclodextrin (CD) homo- and heterodimers is presented. A microwave-promoted Huisgen 1,3-dipolar cycloaddition will efficiently link together monoazido and monoacetylenic CD derivatives through a 1,2,3-triazole bridge. This well-known click reaction provides a versatile method to yield 'head-to-tail' and 'tail-to-tail' CD dimers in a broad range of combinations. Such an easy access to this kind of molecular architecture may be used to fashion ad hoc tailored CD cavities such as pinching-type structures to be exploited as nanosized reactors or molecular carriers. Preliminary estimates of the relative distances and orientations of the two CD units in each kind of dimer were obtained by molecular dynamics simulations and related calculations.