Square pegs in round holes. Preparation and intramolecular complexation of cubyl substituted β-cyclodextrins† and of an adamantane analogue

Abstract

The reaction of either 1-methoxycarbonyl-4-(4-nitrophenoxycarbonyl)cubane or its dimethyl analogue, 2,3-dimethyl-1-methoxycarbonyl-4-(4-nitrophenoxycarbonyl)cubane, with the primary amine of 6^A-(6-aminohexyl)amino-6^A-deoxy-β-cyclodextrin produces the first cubyl substituted β-cyclodextrins, 6^A-deoxy-6^A-{6-[N-(4-methoxycarbonylcuban-1-ylcarbonyl)amino]hexylamino}-β-cyclodextrin and its dimethyl analogue, respectively, and 4-nitrophenolate. The reaction of 1,4-bis(4-nitrophenoxycarbonyl)cubane with 6^A-(6-aminohexyl)amino-6^A-deoxy-β-cyclodextrin produces the dimer 1,4-bis{6-[N-(6^A-deoxy-β-cyclodextrin-6^A-yl)amino]hexylaminocarbonyl}cubane. ¹H NMR ROESY studies are consistent with the cubyl moiety of each of the above three cubyl-substituted β-cyclodextrins complexing in the β-cyclodextrin annuli in D₂O. The reaction of 1-(4-nitrophenoxycarbonyl)adamantane with β-cyclodextrin produces 6^A-{6-[N-(1-adamantylcarbonyl)amino]hexylamino}-6^A-deoxy-β-cyclodextrin which shows a strong intramolecular complexation of its adamantyl moiety. Adamantane-1-carboxylate forms intermolecular complexes with the above three cubyl-substituted β-cyclodextrins in D₂O solution and excludes the cubyl moiety from the β-cyclodextrin annulus. However, this does not occur for 6^A-{6-[N-(1-adamantylcarbonyl)amino]hexylamino}-6^A-deoxy-β-cyclodextrin where intramolecular complexation appears to be sufficiently strong to prevent intermolecular complexation of adamantane-1-carboxylate.