Conformation of ergopeptam and ergopeptine alkaloids (ergocristam and ergocristine)

S. Pakhomova, University of Chemistry and Technology, Prague
J. Ondráček, University of Chemistry and Technology, Prague
M. Hušák, University of Chemistry and Technology, Prague
B. Kratochvíl, University of Chemistry and Technology, Prague
A. Jegorov, Teva Pharmaceutical Industries Ltd.
L. Cvak, Teva Pharmaceutical Industries Ltd.
P. Sedmera, Institute of Microbiology of the Academy of Sciences of the Czech Republic
V. Havlíček, Institute of Microbiology of the Academy of Sciences of the Czech Republic

Abstract

The crystal structures of two ergot alkaloids ergocristam (I) and ergocristine acetone solvate (II), have been determined by X-ray diffraction and compared with their conformation in solution obtained from NMR data. The presence of D-proline in I essentially influences the conformation of the alkaloid tripeptide moiety which seems likely to explain why I does not undergo further enzymatical hydroxylation and is found as a terminal step of ergot alkaloid biosynthesis.