Synthesis and crystal structure determination of cyclosporin H

Alexandr Jegorov, Galena A.s.
Ladislav Cvak, Teva Pharmaceutical Industries Ltd.
Aleš Husek, Teva Pharmaceutical Industries Ltd.
Petr Šimek, Institute of Entomology, Biology Centre of the Academy of Sciences of the Czech Republic
Anna Heydová, Institute of Entomology, Biology Centre of the Academy of Sciences of the Czech Republic
Jan Ondráček, University of Chemistry and Technology, Prague
Svetlana Pakhomova, University of Chemistry and Technology, Prague
Michal Hušák, University of Chemistry and Technology, Prague
Bohumil Kratochvíl, University of Chemistry and Technology, Prague
Petr Sedmera, Institute of Microbiology of the Academy of Sciences of the Czech Republic
Vladimír Havlíček, Institute of Microbiology of the Academy of Sciences of the Czech Republic

Abstract

Acid-catalyzed degradation of cyclosporin A was studied in various solvents and products of reaction were monitored by HPLC. Identification of amino acids and their chirality were determined after hydrolysis and derivatization by GC-MS. Cyclosporin H was isolated as the principal product and its structure was determined by X-ray diffraction: Cyclosporin H-diethyl ether-water (1 : 0.5 : 1) crystallizes in the monoclinic space group 12 with a = 12.338(2) Å, b = 18.963(2) Å, c = 34.074(3) Å, β = 96.47(2)°, Z = 4, and V = 7 921.4(17) Å3.