SELECTIVE FUNCTIONALIZATION AND FLEXIBLE COUPLING OF CYCLODEXTRINS ATTHE SECONDARY HYDROXYL FACE

Methods are described for the chemo- and regioselective monofunctional ization of the secondary hydroxyl face of cyclodextrins. Monofunctiona lization takes place either by nucleophilic epoxide opening of -tert-b utyldimethylsilyl)-(2(A)S)-beta-cylodextrin by ethylenediamine, lithiu m azide, or ammonia or by direct monoalkylation of one of the C(2)-hyd roxyl groups of heptakis(6-O-tert-butyldimethylsilyl)cyclodextrins wit h primary alkyl bromides, with cyano-, ethynyl-, or ester-containing f unctional groups. The latter route enables the synthesis of kis(6-O-te rt-butyldimethylsilyl)-beta-cyclodextrin and its 2-aminomethyl isomer. These are lipophilic precursors for cyclodextrin derivatives having o ne reactive functional group and an enlarged molecular cavity formed b y partial methylation of the secondary hydroxyl face. The direct monoa lkylation route of the secondary face leaves the structure of the cavi ty intact, while this is distorted in the route using nucleophilic epo xide opening. Two amino-functionalized cyclodextrins were used for cou pling reactions with a monofunctionalized calix[4]arene. In this way w ater-soluble cyclodextrin derivatives could be obtained of which the s econdary faces were flexibly capped with a calix[4]arene moiety.