Synthesis of cationic single-isomer cyclodextrins for the chiral separation of amino acids and anionic pharmaceuticals.
We describe a protocol for the synthesis of mono-6(A)-(1-butyl-3-imidazolium)-6(A)-deoxy-beta-cyclodextrin chloride (BIMCD), a cationic, water-soluble cyclodextrin used in the chiral separation of amino acids and anionic pharmaceuticals by capillary electrophoresis. Starting from commercially available chemicals, BIMCD is synthesized in five steps. The first step involves a nucleophilic substitution between p-toluenesulfonyl chloride and imidazole to afford 1-(p-toluenesulfonyl)imidazole (A). In the second step, a nucleophilic substitution between beta-cyclodextrin and A affords mono-6(A)-(p-toluenesulfonyl)-6(A)-deoxy-beta-cyclodextrin (B). In the third step, a nucleophilic substitution between 1-bromobutane and imidazole affords 1-butylimidazole (C). In the fourth step, a nucleophilic addition between A and C affords BIMCD tosylate. In the final step, anion exchange using an ion-exchange resin yields BIMCD as a highly water-soluble solid. Each step takes up to 2 d, including the time required for product purification. The overall protocol requires approximately 6 d.
Tang
Weihua
W
Department of Chemistry, National University of Singapore, Singapore 117543, Singapore. wh-tang@imre.a-star.edu.sg
Ng
Siu-Choon
SC
D000596:Amino Acids / Q000737:chemistry*; D000838:Anions; D002412:Cations; D003505:Cyclodextrins / Q000138:chemical synthesis*; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*
D000596:Amino Acids; D000838:Anions; D002412:Cations; D003505:Cyclodextrins; D004364:Pharmaceutical Preparations; C526580:mono-6A-(1-butyl-3-imidazolium)-6A-deoxycyclodextrin