Collect. Czech. Chem. Commun. 1999, 64, 89-98

Crystal Structures of Cyclosporin Derivatives: O-Acetyl-(4R)-4-(E-2-butyl)-4,N-dimethyl-L-threonyl-cyclosporin A and O-Acetyl-(4R)-4-[E-2-(4-bromobutyl)]-4,N-dimethyl-L-threonyl-cyclosporin A

Bohumil Kratochvíla, Alexandr Jegorovb,*, Svetlana Pakhomovaa, Michal Hušáka, Petr Bulejc, Ladislav Cvakc, Petr Sedmerad and Vladimír Havlíčekd

a Department of Solid State Chemistry, Prague Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic
b Galena Co., Research Unit, Branišovská 31, 370 05 České Budějovice, Czech Republic
c Galena Co., R. D., 747 70 Opava-Komárov, Czech Republic
d Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic


The structures of O-acetyl-(4R)-4-(E-2-butyl)-4,N-dimethyl-L-threonyl-cyclosporin A (1) and O-acetyl-(4R)-4-[E-2-(4-bromobutyl)]-4,N-dimethyl-L-threonyl-cyclosporin A (2) were determined by X-ray diffraction methods and compared with the structure of related cyclosporins. In contrast to expectation, neither the acetylation nor the subsequent bromination of 1 affects the conformation and packing of cyclosporins in the solid state. Both compounds are isomorphous and crystallize in the orthorhombic space group P212121 with a = 12.936(2) Å, b = 15.590(2) Å, c = 36.280(3) Å, and a = 12.916(3) Å, b = 15.675(4) Å, c = 36.715(7) Å, for 1 and 2, respectively.

Keywords: Cyclic peptides; Cyclosporins; Crystal structure determination; X-Ray diffraction; NMR spectroscopy; Immunosupressants.