Anna K. Przybył

The Stereochemistry of the Reduction of Cyclic Enaminones

Summary. The stereo- and regiochemistry of di-, tri-, and tetracyclic enaminones upon catalytic hydrogenation on Pd and Pt catalysts seems to be mainly a function of the catalyst and the medium. The highest stereoselectivity was observed for multiflorine on Pd/C in which 99% of equatorial alcohol were formed in this case, the formation of alcohols proceeds via a ketonic intermediate. On platinum, irrespective of the solvent used (EtOH, H2O, AcOH, HCl), the hydrogenation reaction proceeds through ketonic (piperidone system) and dehydro (pyridone system) intermediates. In EtOH or H2O solution, the dehydro product remains unchanged, whereas the ketonic intermediate is reduced to a mixture of epimeric alcohols. In HCl and acetic acid, both intermediates are hydrogenolyzed to a product with a methylene group, but the ketonic one is additionally reduced to a mixture of epimeric alcohols. Reductions with complex metal hydrides provide mixtures of epimeric alcohols with a predominance of equatorial orientation. The structures of products were determined by NMR spectroscopy and/or by GC-MS analysis.

The structure of angustifoline, an alkaloid ofLupinus angustifolius, in solution

SummaryThe1H and13C NMR spectra of the lupin alkaloidangustifoline1 in four solvents (cyclohexane-d12, CDCl3, CD3CN, and C6D6) were assigned using 2D H,H and H,C COSY and 2D J-resolved spectra. The torsional HCCH angles calculated from the vicinalJHH coupling constants are essentially in agreement with those expected for the deformed all-chair conformation withendo oriented N(12)-H bond, reported earlier for1 in the solid state. Some arguments seem to point, however, to a small contribution of other conformations: with ring A deformed in another direction, deformed all-chair withexo oriented N(12)-H bond and/or a conformation with ring C in the boat form.ZusammenfassungDie1H- und13C-NMR Spektren des Lupinalkaloids Angustifolin (1) in vier Lösungsmitteln (Cyclohexan-d12, CDCl3, CD3CN und C6D6) wurden mit Hilfe von H,H-COSY-, C,H-COSY und 2D-J-aufgelösten Spektren zugeordnet. Die aus den vicinalen Kopplungskonstanten berechneten Torsionswinkel stimmen mit den für eineall-chair Konformation mitendo-orientierter N(12)-H-Bindung erwarteten und für1 im festen Zustand bereits berichteten überein. Es liegen allerdings auch Hinweise auf geringe Beiträge anderer Konformationen vor: deformierter Ring A, verformteall-chair-Konformation mitexo-orientierter N(12)-H-Bindung und/oder Boot-Konformation von Ring C.

Regio-selective bromination of multiflorine and structures of 3-bromomultiflorine and its molecular complex with succinimide

Abstract The regio-specific bromination of multiflorine, an alkaloid isolated from Lupinus albus is described. The bromomultiflorine and its molecular complex with succinimide have been characterized by IR and NMR spectroscopy, as well as by X-ray diffraction. The conformation in solution and in the solid state has been determined. The molecular complex formation between 3-bromomultiflorine and succinimide molecules is the first case in the class of lupine alkaloids. Both molecules of this complex are held together by an intermolecular hydrogen bond NH⋯N which leads to a conversion of alkaloid nitrogen atom configuration. As a consequence, ring C adopts a chair conformation, whereas it is in a boat form in 3-bromomultiflorine.

Complexing ability of (−)-cytisine — Synthesis, spectroscopy and crystal structures of the new copper and zinc complexes

For the first time the NMR spectra of quinolizidine alkaloid with Cu(II) are studied. Structures of new complexes of (-)-cytisine with Cu(+2) and Zn(+2) cations are visualized, discussed in detail and characterized by spectroscopic methods: ESI-MS, NMR, UV-vis, EPR and crystallographic methods. In solution metal coordinates through the protonated nitrogen atoms of secondary amino groups (in piperidine ring) of cytisine molecule. While in solid state the most stable structures of the complexes are those in which the coordination of Cu(II) and Zn(II) salts is realized solely through the lactam carbonyl oxygen atom.

Spectral and Photophysical Behavior of Cytisine in n-Hexane. Experimental Evidence for the S1(n,π*) → S0 Fluorescence

Spectral and photophysical properties of (-)-cytisine (the compound used as a smoking cessation aid and a potential drug in Alzheimers and Parkinsons diseases) were investigated. The two conformers of cytisine, whose presence in the S0 state has been earlier proved by the NMR and IR methods as well as in theoretical calculation, in nonpolar n-hexane show a rarely observed prompt fluorescence from the S1(n,π*) excited state. This observation is unambiguously evidenced by very small radiative rate constants of these two emitting conformers, kF = 7.4 × 105 and 3.0 × 105 s-1. Their lifetimes in the S1(n,π*) state are relatively long, τS1 = 1.9 and 6.7 ns; therefore, their fluorescence quantum yield is relatively high ϕF ∼ 10-3. The long-wavelength band in the cytisine absorption originates from the excitation to the S2(π,π*) state, while the S1(n,π*) state is not observed in this spectrum. Thus, the excited state S2(π,π*) is manifested only in the absorption spectrum, while the excited state S1(n,π*) is seen only in the fluorescence spectrum, so cytisine in n-hexane is characterized by close lying (n,π*) and (π,π*) excited singlet states.

Spectral and photophysical properties of cytisine in acetonitrile – Theory and experiment

Spectral and photophysical properties of (-)-cytisine that is used as a smoking cessation aid, and which derivatives are promising tools in a treatment of neurological diseases, were investigated in acetonitrile, non-specifically interacting solvent with a polarity similar to water. The two chair conformers of cytisine were found the most stable in the ground state S0 and the lowest excited singlet state S1(π,π*), wherein axial one was characterized by a significantly larger abundance, fluorescence lifetime 0.15 ns and fluorescence quantum yield 0.008. The S1(π,π*) excited state of both cytisine conformers deactivated almost exclusively via internal conversion.

The amide protonation of (-)-N-benzoylcytisine in its perchlorate salts

The (13)C NMR spectrum of (-)-N-benzoylcytisine perchlorate does not show a double set of signals typical of amide compounds, although this effect has been observed for the other diamine derivatives of cytisine. This observation means that in solution there must be the state of equilibrium between two forms of the cation with the protonated amide groups. DFT calculations have indeed indicated two preferred tautomeric forms with protonated oxygen atoms of amide groups. In the solid state however, according to X-ray analysis of perchlorate and perchlorate hydrate of N-benzoylcytisine the oxygen atom of the amide group in the six-membered ring A is preferred protonation site as compared with the oxygen in benzoic moiety. (-)-N-benzoylcytisine salt is the first compound from among the known derivatives of quinolizidine alkaloids that are not N-oxides, in which in solid state only the oxygen atom at cyclic amide is protonated instead of nitrogen atom or oxygen in benzoic moiety.

N-Methyl-2-thio­cytisine

The rings of the three-ring cytisine system in the title compound [systematic name: (1R,5S)-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido[1,2-a][1,5]diazocine-8-thione], C12H16N2S, have planar [maximum deviation 0.0170 (7) Å], half-chair and chair conformations. In the crystal structure, relatively short and directional C—H⋯π interactions and weaker secondary C—H⋯S contacts join the molecules into helical chains along the [001] direction.