Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins
Laszlo Jicsinszky1, Marina Caporaso1, Katia Martina1
1Department of Drug Science and Technology and NIS - Centre for Nanostructured Interfaces and Surfaces, University of Turin, Via P. Giuria 9, 10125 Turin (Italy).
Abstract:
A number of per-6-substituted cyclodextrin derivative syntheses have been effectively carried out in a planetary ball mill under solvent-free conditions. The preparation of Bridion® and important per-6-amino/thiocyclodextrin intermediates without polar aprotic solvents, a source of byproducts and persistent impurities, could be performed. Isolation and purification processes could also be simplified. Considerably lower alkylthiol/halide ratio were necessary to reach the complete reaction in comparison with thiourea or azide reactions. While the presented mechanochemical syntheses were carried out on the millimolar scale, they are easily scalable.
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