Regioselective Double Capping of Cyclodextrin Scaffolds

Four different regioselective double capping reactions were applied either to alpha- or beta-cyclodextrin (CD) scaffolds. The first, which relied on the use of a rigid, bulky dialkylating reagent containing two trityl-like subunits, gave access to an A,B,D,E-tetra-functionalised beta-CD regioisomer in large scale reactions. Two further capping reactions, involving the dianions PhP2- and S2-, led to the synthesis of new C-1-symmetrical beta-cyclodextrins in which pairs of neighbouring glucose units are linked by very short spacers. The last double capping reaction described allowed the high-yield preparation of unprecedented alpha- and beta-cyclodextrins containing two sulfate handles. Proximal capping turned out to be favoured for each of the above difunctional reagents. The structural characterisation of the capped species was achieved by thorough NMR investigations as well as by single-crystal X-ray diffraction studies.