A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of alpha-, beta-, and gamma-cyclodextrin with 1, 2, and 3 permanent positive charges
Abstract
An efficient synthetic route toward the preparation of a complete series of monosubstituted tetraalkylammonium cyclodextrin (CD) derivatives is presented. Monotosylation of native CDs (alpha-, beta-, gamma-) at position 6 gave the starting material.
Reaction of monotosylate (mono-Ts-CD) with 45% aqueous trimethylamine gave CDs substituted with one cationic functional group in a single step. Derivatives equipped with a substituent containing two cationic sites separated by an ethylene or a propylene linker were prepared by reacting mono-Ts-CD with neat N,N,N'-trimethylethane-1,2-diamine or N,N,N'-trimethylpropane-1,3-diamine and subsequent methylation by CH3I in good yields.
Finally, analogues bearing a moiety with three tetraalkylammonium sites were synthesized by reacting mono-Ts-CD with bis(3-aminopropyl) amine and subsequent methylation. The majority of the presented reactions are very straightforward with a simple work-up, which avoids the need of chromatographic separation.
Thus, these reactions are suitable for the multigram-scale production of monosubstituted cationic CDs.