A systematic comparative study of the conformational dynamics of lupinine and epilupinine, two 1-hydroxymethyl quinolizidine epimers, as a function of phase transition and of their protonation is presented. Lupinine and epilupinine have a trans-quinolizidine configuration and they differ only in the position of the CH2OH group. The axial position of this group allows the formation of an intramolecular hydrogen bond OH … N in lupinine, in contrast to epilupinine in which this group is in the equatorial position. Intrinsic conformational equilibria for both epimers have been defined. Despite the significant difference in the population of the preferred rotamers of lupinine and epilupinine, both epimers adopt very similar crystal structures, but in all other states and forms, e.g., pure liquids, solutions in inert and polar solvents, and protonated salts, they behave in drastically different ways.
