Novel Amphiphilic Cyclodextrins: Graft-Synthesis of Heptakis(6-alkylthio-6-deoxy)-β-cyclodextrin 2-Oligo(ethylene glycol) Conjugates and Their ω-Halo Derivatives

Novel amphiphilic cyclodextrins were synthesised by grafting oligo(ethylene glycol) units onto the secondary side of heptakis(6-alkylthio-6-deoxy)-β-cyclodextrins (alkyl = ethyl, hexyl, dodecyl and hexadecyl). The oligo(ethylene glycol) substituents were introduced by reaction of heptakis(6-alkylthio-6-deoxy)-β-cyclodextrins with ethylene carbonate in the presence of potassium carbonate at elevated temperatures. The resulting oligo(ethylene glycol)-cyclodextrin conjugates were characterised by 1H NMR and 13C NMR, COSY and HSQC spectroscopy, and mass spectrometry. Addition of ethylene carbonate occurs exclusively at OH2 and results in a degree of substitution of 8−22 ethylene glycol units per cyclodextrin. Also, the ω-bromo and ω-iodo derivatives of heptakis[6-deoxy-6-hexylthio-2-oligo(ethylene glycol)]-β-cyclodextrin were prepared as strategic synthetic intermediates. The observation that seven halogen atoms are introduced per cyclodextrin provides strong evidence for the grafting of oligo(ethylene glycol) to each of the seven glucose units in the cyclodextrin ring.