Theoretical and experimental studies on the molecular and electronic structures of cytisine and unsaturated keto-sparteines

Abstract Density functional theory calculations with the B3LYP hybrid functional have been performed to determine the equilibrium structures of cytisine, N -methylcytisine, multiflorine, 5,6-didehydromultiflorine, anagyrine, thermopsine, 5,6-didehydrolupanine, and aphyllidine. These molecules, except cytisine, multiflorine, and aphyllidine, exhibit a marked preference for one conformation with the ring C chair. Cytisine, which also adopts the ring C chair, is predicted to exhibit the endo/exo conformational equilibrium of the N–H group in the gas phase or solution. Multiflorine is instead found to exist as a mixture of C-boat and C-chair conformers in the gas phase or solution. The most stable ( C-chair ) conformer of aphyllidine shows a marked conformational flexibility, with the exo and endo wings of ring A being nearly isoenergetic. The electronic structures of these quinolizidine alkaloids have been studied by measuring and calculating significant features of their NMR and photoelectron spectra. In particular, a representative set of NMR chemical shifts and nuclear spin–spin coupling constants, calculated by means of DFT formalisms, compares favourably with experiment. Notably, the repercussion of stereoelectronic hyperconjugative effects on Δ δ (H eq /H ax ) and Δ 1 J (CH eq /CH ax ) of the 〉N–CO– groups is correctly accounted for by the DFT results. Based on ab initio outer valence Green’s function calculations, a reliable interpretation of the uppermost bands in the photoelectron spectra has been advanced. The theoretical results indicate a complex interaction of the n (N), n (O), π (N), π (CO), and π (CC) chromophores. The lowest-energy conformations of all compounds allow a consistent interpretation of the photoelectron spectra. The conformational equilibrium in the gas phase is partially revealed by the photoelectron spectrum of multiflorine but not by that of cytisine. The single-crystal X-ray structure was also determined for anagyrine hydrochloride hydrate.