Alkaloids, nuphar

The structure of nupharamine is obviously very close to that of the quinolizidine alkaloids which also occur in Nuphar species (see Chap.38) and, for example, it is possible to degrade the quinazoline, alkaloid nupharidine (71) to (-)-nupharamine via the enamine (72) (R.T. LaLonde et al., 

Miscellaneous piperidines and pyridines from plant sources 

A new alkaloid from Conium species is w-methylpseudoconhydrine (75) (M.F. Roberts and R.T. Brown, Phytochem., 1981, 20, 

It shows a strong similarity to some of the Cassia-type bases. Several stereoselective syntheses of pseudoconhydrine have been reported (T. Shono et al., Chem.Letters, 1984, 1101 1129 G.VJ.J. Fleet, M.J. Gough and P.VJ. Smith, Tetrahedron Letters, 1984, 25, 1853). ( )-a-Conhydrine (76) 

The spiro piperidine (77) is a constituent of the seeds of the leguminous plants Lonchocarpus sericeus and L. costaricensis (L.E. Fellows et al., Chem.Comm., 1979, 977), and the simple phenacylpiperidine (78) is an antifungal agent from the plant Boehermia cyclindrica (W. Dopke et al., Z.Chem., 1981, 21, 358). Other piperidines include dumetorine (79), which is obtained from the yam Pioscorea dumetorum (D.G. Corley, M.S. Tempesta and M.M. Iwu, Tetrahedron Letters, 1985, 26, 1615), and the simple glucoside (80) an extractive of Xanthocercis zambesiaea (S.V. Evans et al., ibid., p 1465). 

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Joseph P.A. Harrity of the University of Sheffield has reported (J. Org. Chem. 2005, 70, 207) a complementary approach to enantiomerically-pure piperidines. Alkylated azridines such as 17 are readily available from aspartic acid. Pd-catalyzed condensation of 17 with the Trost reagent 18 was found to be most effectively mediated by bis-phosphines such as dppp , 1,3-bis-diphenylphosphinopropane. The piperidine 19 was the key intermediate for the preparation of several of the Nuphar alkaloids, including 20. 

C NMR spectra of nine Nuphar alkaloids and of model compounds have been reported. (157) Reference to the spectra of deoxynupharidine [233], 7-epideoxynupharidine [234], and the thiomethylquinolizidines [235] and [236] illustrates the low frequency absorption of axial 13CH3 and axial 13CH2SMe nuclei in trans fused quinolizidine derivatives... 

The two previous reviews of Nuphar alkaloids published in this treatise covered the literature up to 1974 (7). Since then, 21 new alkaloids have been isolated and characterized. Most of these are simple variants of already known structures, and only in one case has a different ring system been discovered. 

For the first time, the chemistry of Nuphar alkaloids has been characterized in greater detail. The ring systems present in this group of alkaloids continue to... 

New Nuphar alkaloids isolated since 1974 are listed in Table I. Table 1 includes monomeric CIS alkaloids and dimeric sulfur-containing alkaloids. 

Furyl)-8-methyloctahydroindolizine (4) was isolated from Castor fiber L. and is the first example of a Nuphar alkaloid with an indolizine chromophore (26). Structure 4 was proposed by the examination of mass spectra. 

Nupharolidine (9) was isolated from Nuphar lutea (28). Its structure was determined by IR, 1H-NMR, and mass spectroscopy. Compound 9 was the first example of a Nuphar alkaloid with a hydroxyl group in the quinolizidine system. This alkaloid is isomeric with castoramine (59), nuphamine, and isocastora-mine (10). 

In the last decade more chemical attention has been focused on those Nuphar alkaloids which contain sulfur. The chemical behavior of this group is very much dependent on the presence of sulfur. Sulfur introduces additional steric hindrance to the molecule, creates a new nucleophilic center, and increases the stability of carbanions in sulfoxides the C—S bond in sulfonium salts is strongly polarized. 

Scheme 4. Deuteration of iminium salts of Nuphar alkaloids.

The quatemization of nitrogen and/or sulfur seems to be more dependent on steric hindrance and stereochemistry around the sulfur atom different products are obtained in the series of alkaloids with equatorial sulfur as compared with those in which sulfur is axial. Thiobinupharidine (16) (sulfur equatorial) can be easily quatemized on nitrogen, resulting in only isomeric mono- or dimethiodides (57). In this reaction, partial trans-cis transformation of the quinolizidine ring was observed. This isomerization seems to be influenced by the presence of sulfur and does not follow the pattern observed for the C,5 Nuphar alkaloids (41) where direct dependence on the configuration of C-7 is controlling. No methyla-... 

Scheme 9. Routes for the synthesis of Nuphar alkaloids from nitrones.

C-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... 

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