Spectroscopy of Nuphar Alkaloids

13C-NMR spectrometry has assumed a very efficient role in the determination of the structure and stereochemistry of Nuphar alkaloids and their derivatives. Accurate assignments of chemical shift values to particular carbon atoms in the molecules and clear changes in chemical shift values of particular carbon atoms, owing to conformational transformations, are well within the rules generally accepted for I3C-NMR spectroscopy, which facilitates identification of the signals in the l3C-NMR spectra. 

For the C, 5 Nuphar alkaloids containing quinolizidine rings, deoxynupharidine (14), 7-epideoxynupharidine (15), nupharolutine (50), and 7-epinupharolutine (60), and also for the synthetic model compounds 3(e)-methyl-3(a)-methylthio-methylquinolizidine (68) and 3(a)-methyl-3(e)-methylthiomethylquinolizidine (69), the diagnostic carbon atoms that determine the conformation of the methyl and methylthiomethyl substituents are the carbon atoms of those groups as well as the carbon atoms of the quinolizidine ring at which the substituents are situated (67). For substituents in an axial conformation, the above-mentioned carbon 

Different changes are observed when quaternization causes inversion of the quinolizidine ring from trans to cis, as is observed in the case of nupharidine (which is an N-oxide) (32) and deoxynupharidine methiodide (71) (41, 69). In such cases the tertiary carbon atoms in the 3 position (C-4, C-10) with respect to the new N+—O or N+—C bonds exhibit a paramagnetic shift, and the secondary carbon atom (C-6) exhibits a diamagnetic shift in comparison with similar carbon atoms in the free base. 

The change of conformation of the N-substituted quinolizidine ring from trans to cis (as a result of quaternization of nitrogen) causes a change of stereochemistry of C-7 or C-7. In consequence, C-17 changes from a diaxial relationship in thiobinupharidine (16) to an axial-equatorial one or, in the case of cis-AB, cis-A B thiobinupharidine dimethiodide (41), to an equatorial-equatorial relationship. This causes a signal shift for C-17 downfield by 5 and 10 ppm, respectively (43). 

Similarly, as in the case of quaternary salts of C, 5 Nuphar quinolizidinium alkaloids, the diagnostic carbon atoms apart from C-17 for the quaternary salts of dimeric Nuphar alkaloids are those situated a with respect to the quaternary nitrogen atom and the N+-methyl group. In the case of thiobinupharidine methio- 

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