Square pegs in round holes. Preparation and intramolecular complexation ofcubyl substituted beta-cyclodextrins and of an adamantane analogue

The reaction of either 1-methoxycarbonyl-4-(4-nitrophenoxycarbonyl)cubane o r its dimethyl analogue, 2,3-dimethyl-1-methoxycarbonyl-4-(4-nitrophenoxyca rbonyl)cubane, with the primary amine of 6(A)-(6-aminohexyl)amino-6(A)-deox y-beta-cyclodextrin produces the first cubyl substituted beta-cyclodextrins , 6(A)-deoxy-6(A)-{6-[N-(4-methoxycarbonylcuban-1-ylcarbonyl)amino]hexylami no}-beta-cyclodextrin and its dimethyl analogue, respectively, and 4-nitrop henolate. The reaction of 1,4-bis(4-nitrophenoxycarbonyl)cubane with 6(A)-( 6-aminohexyl)amino-6(A)-deoxy-beta-cyclodextrin produces the dimer 1,4-bis{ 6-[N-(6(A)-deoxy-beta-cyclodextrin-6(A)-yl)amino]hexylaminocarbonyl}cubane. H-1 NMR ROESY studies are consistent with the cubyl moiety of each of the above three cubyl-substituted beta-cyclodextrins complexing in the beta-cyc lodextrin annuli in D2O. The reaction of 1-(4-nitrophenoxycarbonyl)adamanta ne with beta-cyclodextrin produces 6(A)-{6-[N-(1-adamantylcarbonyl)amino]he xylamino}-6(A)-deoxy-beta-cyclodextrin which shows a strong intramolecular complexation of its adamantyl moiety. Adamantane-1-carboxylate forms interm olecular complexes with the above three cubyl-substituted beta-cyclodextrin s in D2O solution and excludes the cubyl moiety from the beta-cyclodextrin annulus. However, this does not occur for 6(A)-{6-[N-(1-adamantylcarbonyl)a mino]hexylamino}-6(A)-deoxy-beta-cyclodextrin where intramolecular complexa tion appears to be sufficiently strong to prevent intermolecular complexati on of adamantane-1-carboxylate.