A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges.

Martin Popr,Simona Hybelbauerová,Jindřich Jindřich

doi:10.3762/bjoc.10.142

Abstract

An efficient synthetic route toward the preparation of a complete series of monosubstituted tetraalkylammonium cyclodextrin (CD) derivatives is presented. Monotosylation of native CDs (α-, β-, γ-) 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.

Highlights

Cyclodextrins (CDs) are cyclic oligosaccharides with the shape of a hollow truncated cone, first described in 1891 by Villiers [1]
This article presents the synthesis of a complete series of monosubstituted CD derivatives with a permanent positive charge (Figure 1)
The most crucial and scope-limiting step of the reaction sequence was the introduction of a suitable leaving group in the position 6 of the native CD

Summary

Introduction

Cyclodextrins (CDs) are cyclic oligosaccharides with the shape of a hollow truncated cone, first described in 1891 by Villiers [1]. Many different CD derivatives have been described in the literature, but most of the preparations suffer from the polydispersity of the products, low yields and poor selectivity due to the large number of hydroxy groups. Reactions employing one equivalent of derivatizing agent along with an excess of base lead to the 6I-O-substituted products, while the preparation of 2I-O-substituted derivatives [15] takes advantage of the highest acidity of 2-OH hydroxy groups.

Results

Conclusion