A Conformational Study of Lysergic Acid and iso-Lysergic Acid Dialkylamides by Proton Magnetic Resonance Spectroscopy

Abstract

The 220 MHz p.m.r. spectra of the dimethylamides of D-lysergic acid (3) and D-iso-lysergic acid (4) are reported. Extensive use of double resonance experiments and the presence of four long-range coupling constants provide an unambiguous assignment for the conformation of 3 in CDCl3. Its D ring is shown to exist in a half-chair form in which the 8-β amide function is pseudo-equatorial. Its epimer essentially exists in the other half-chair form with a pseudo-equatorial 8-α amide function. Data from the p.m.r. spectra of a series of N,N-dialkylamides of these acids are also presented.The spectrum of protonated 3 at 23 °C shows two forms of the 6-NCH3 and 8-CON(CH3)2 groups but only one for the epimer 4.