Efficient synthesis of pure monotosylated beta-cyclodextrin and its dimers.
6-O-Monotosyl-β-cyclodextrin (mono-Ts-βCD) is one of the most important intermediates in the production of substituted βCD. So far, performing the monotosylation reaction and, in particular, the purification steps was challenging, relied on toxic solvents, and resulted in long and expensive procedures at, importantly, low yields. Here, the reaction of cyclodextrin with p-toluenesulfonyl chloride in aqueous environment is described to obtain a highly pure mono-Ts-βCD, for which a single-step purification with a cation exchange resin was applied. With this synthetic route and purification, yields could be increased from typically <10-15% to 35%, and organic solvents could be avoided. As characterized by FTIR, mass spectrometry, elemental analysis, and NMR, mono-Ts-βCD was obtained with a molar purity of >98mol%. From mono-Ts-βCD, β-cyclodextrin dimers linked by ethylenediamine (bis-Et-βCD) were successfully prepared (yield 93%, purity 96mol%) in a one-step approach using an anion exchange resin to trap leaving groups that typically interfere in the reaction. This synthesis procedure with a direct collection of side-products may be a general strategy applicable for nucleophilic substitution of tosylated cyclodextrins.
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany.
Giuseppe
G
Tripodo
Christian
C
Wischke
Axel T
AT
Neffe
Andreas
A
Lendlein
D019281:Dimerization; D015394:Molecular Structure; D014105:Tosyl Compounds / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry
D014105:Tosyl Compounds; D047392:beta-Cyclodextrins; C031215:betadex
Ion exchange resin; Monotosyl β-cyclodextrin; β-Cyclodextrin; β-Cyclodextrin dimer