Conformational Analysis of the D Ring of Lysergic Acid Amides and its Bioactive Conformation

Sa？etak 1H, 13Cnuclear magnetic resonance data on simple lysergic acid amides and ergopeptines indieate eonsiderable flexibility of the D ring. The actual conformation depends upon the existence (or absence) of intramolecular hydrogen bonding between N6 and the central amide N20-H group. The results are in agreement with molecular mechanics calculations. The proposal for the bioactive conformation is based on the comparison of key geometric parameters of the possible ergolene conformers with ones derived for the conformationally restricted dopamine congeners