Size discrimination in intramolecular complexation of modified a-cyclodextrins: a preparative and nuclear magnetic resonance study

Abstract

Acylation of the primary amine group of 6A-(6-aminohexylamino)-6A-deoxy-α-cyclodextrin 1 by 4-nitrophenyl trinorbornane-2-acetate 6, 1-methoxycarbonyl-8-(4-nitrophenoxycarbonyl)cubane 7, 1-methoxycarbonyl-2,3-dimethyl-8-(4-nitrophenoxycarbonyl)cubane 8, and 1-(4-nitrophenoxycarbonyl)adamantane 9, respectively, gives 6A-deoxy-[6-(trinorbornan-2-ylacetylamino)hexylamino]-α- cyclodextrin 2, 6A-[6-(8-carboxycuban-1-ylcarbonyl-amino)hexylamino]-6 A-deoxy-α-cyclodextrin 3, 6A-[6-(8-carboxy-2,3-dimethylcuban-l-ylcarbonylamino)hexylamino]- 6A-deoxy-α-cyclodextrin 4, and 6A-[6-(adamantan-1-ylcarbonylamino)hexylamino]-6A- deoxy-α-cyclodextrin 5, in good yields together with 4-nitrophenolate. In basic D2O, the substituents of 1-4 complex intramolecularly within the α-cyclodextrin annulus, whereas that of 5 does not due to its larger size, as shown by 1H ROESY NMR spectroscopy. This facilitates a mechanistic comparison with the formation of βCD analogues of 2-5.