Cyclosporins of symmetry P2₁ - A series of clathrates

Alexandr Jegorov, Teva Pharmaceutical Industries Ltd.
Svetlana Pakhomova, University of Chemistry and Technology, Prague
Michal Hušák, University of Chemistry and Technology, Prague
Bohumil Kratochvíl, University of Chemistry and Technology, Prague
Zdirad Žák, Masaryk University
Ladislav Cvak, Teva Pharmaceutical Industries Ltd.
Martin Buchta, Teva Pharmaceutical Industries Ltd.

Abstract

A series of isomorphous clathrates (cyclosporin A: solvent = 1 : 1) is reported. The structure of the tetrahydrofuran (1) and dibutylether (2) clathrates have been determined by X-ray single crystal diffraction. The cyclosporin molecules in both structures are associated via van der Waals interactions forming cavities occupied by solvent molecules. The structure refinement based on room-temperature data sets show significant disorder of the side chains of the cyclosporin A molecule with no adequate model of the solvent molecule in both structures. In contrast, the position of dibutylether was successfully localised using a low-temperature data set for 2.