Structural characterization of 2-bromo-aci-ergokryptinine

B. Klepetarova,¹ J. Cejka,¹ B. Kratochvil,¹ L. Cvak,² A. Jegorov^3,*

¹Department of Organic Structure Analysis, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n. 2, 166 10 Praha 6, Czech Republic

²IVAX Pharmaceuticals, Ostravska 29, 747 70 Opava, Czech Republic

³IVAX Pharmaceuticals, Research Unit, Branisovska 31, 370 05 Ceské Budejovice, Czech Republic

Ergot alkaloid bromocriptine (2-bromo-a-ergokryptine) exhibits several therapeutic effects - it is used in the treatment of Parkinson’s disease, migraine and it is a strong inhibitor of prolactin formation [1]. It is used in the form of its mesylate salt. With regard to its importance, considerable effort has been devoted to its degradation products as potential impurities of the drug substance.

2-bromo-aci-ergokryptinine is one of the possible degradation products of bromocriptine mesylate active substance. It is formed by a combination of two degradation reactions - isomerization in position 8 of ergoline part and isomerization in position 2´ of the peptidic moiety. Whereas isomerization in position 8 of ergoline part is fairly well documented, any crystal structure determination of aci-ergopeptine has apparently not been reported yet.

Two solvatomorphs of 2-bromo-aci-ergokryptinine (bis-acetone solvate and bis-2-butanone solvate) were prepared and their structures were determined by single crystal X-ray diffraction. Their molecular conformations were compared with the structure of active substance bromocriptine mesylate [2].

1. A. Renodon, J. L. Boucher, M. A. Sari, M. Delaforge, J. Ouazzani, D. Mansuy, FEBS Lett., 406, (1997), 33-36.

2. M. Hušák, B. Kratochvíl, A. Jegorov, L. Cvak, Z. Kristallogr., 212, (1997.), 39-40.

Acknowledgements.

The authors are greatly thankful to the Ministry of Education, Youth and Sports of the Czech Republic for the financial support (programme MSM 6046137302).