Quinolizidine alkaloids structure

Cytisine is a tricyclic quinolizidine alkaloid that binds with high affinity and specificity to nicotinic acetylcholine receptors. In principle, this compound can exist in several conformations, but semi-empirical calculations at the AM 1 and PM3 levels have shown that stmctures 19 and 20 are more stable than other possible conformers by more than 50 kcalmol-1. Both structures differ by 3.7 kcalmol 1 at the AMI level and 2.0 kcalmol 1 at the PM3 level, although this difference is much smaller when ab initio calculations are employed <2001PJC1483>. This conclusion is in agreement with infrared (IR) studies and with H NMR data obtained in CDCI3 solution, which are compatible with an exo-endo equilibrium < 1987JP21159>, although in the solid state cytisine has an exo NH proton (stmcture 19) (see Section 12.01.3.4.2). 

In comparison with other spectroscopic methods, 13C-NMR spectroscopy affords the most valuable information for the stereochemical and conformational analysis of quinolizidine compounds. On the basis of the results, summarized in a review by Tourwe and van Binst (313) as well as in a series of publications (314-318), the steric structure elucidation of indolo[2,3-a]quinolizidine alkaloids has been facilitated. 

The common structural feature of quinolizidine alkaloids is a decalin ring system with a nitrogen at one vertex. Often a second or third nitrogen atom is... 

Kinghom, A.D. and Balandrin, M.F. (1984). Quinolizidine alkaloids of the Leguminosae Structural types, analysis, chemotaxonomy and biological activities, in Pelletier, S.W., Ed., Alkaloids chemical and biological perspectives, John Wiley and Sons, New York, pp. 105-148. 

The third structural group of alkaloids, from the same a, are quinolizidine alkaloids (QAs). It is a large group of compounds with very different... 

Tetracyclic quinolizidine alkaloids can be divided into two types, both according to chemical structure and, especially, biological activity. These are tetracychc alkaloids, which contain a quinohzidine nucleus, and others with a pyridone nucleus. Here, the first type of alkaloids (with a quinohzidine nucleus) will be discussed. The second type will be considered in the next sub-chapter as pyridone alkaloids. 

Sophorine was isolated from Sophora alopecuroides (26). The nature of MS decay showed that sophorine is a quinolizidine alkaloid of the lupinine type. The IR spectrum suggests the presence of a franj-quinolizidine moiety (2675-2945 cm ) and an — NH—CO— group (1605 and 1683 cm ). On the basis of chemical shift analysis and signal multiplicity of H- and C-NMR spectra as well as biosynthetic considerations, structure 59 was proposed for sophorine. 

The new alkaloid LC-2 was isolated fiom Lupinus cosentinii (87). It is considered to be a multiflorine derivative, probably an intermediate product in the biosynthesis of the latter alkaloid and occurring in plants together. There are absorption bands at 1580-1625 (——CH=CH—CO— ), 920, and 990 cm (—CH=CH2) in the IR spectrum of this alkaloid. In the H-NMR spectrum there are proton signals presented as doublets at 8 4.92 and 6.86, as in multiflorine (85). Alkaloid LC-2 is converted to desoxyhexahydrorhombifoline (86) by reduction with zinc in 2 N HCl (Scheme 4). Alkaloid LC-2 appears to be a tricyclic quinolizidine alkaloid, and its structure is given by formula 87. 

Our appreciation is expressed to F. Kamayev for assistance in writing Section II, i C-NMR Spectroscopy of Quinolizidine Alkaloids, and to B. Ibragimov for assistance in writing Section III, X-Ray Structural Investigation of Quinolizidine Alkaloids. ... 

Analysis of all the above results led to only two possible structures, A and B, for lythrancines I-IV and lythrancepines I—III. Structure A is preferred because the molecular models show large interactions between the 10-methylene group and the aromatic hydrogen atoms in B and the 13-membered ring is highly strained. X-ray crystallographic studies of lythrancine 101 O-brosylate confirmed stereochemistry A. Thus, the absolute stereochemistry of seven quinolizidine alkaloids was established as 100-103 and 107-109 (104). 

Other isolation studies are summarized in Table l 2-7 five new alkaloids have been obtained this year. Cell suspension cultures of Baptisia australis, Lupinus polyphyllus, and Sarothamnus scoparius produce lower yields of alkaloids than the differentiated plants, with lupanine as the main component8 (cj Vol. 11, p. 63). Examination of the leaf alkaloids of B. australis by g.l.c. and by g.l.c.-m.s. resulted in the identification of eleven constituents, including two new alkaloids.2 The structures and the distribution of some quinolizidine alkaloids that may be used as systematic markers in the Leguminosae have now been supplemented by more recent data.9... 

Bitterness varies with the chemical structure of an alkaloid. With the quinolizidine alkaloids (QAs) the following scale was assessed for man Mean detection levels are 0.00085% for sparteine, 0.0021% for lupanine, and 0.017% for hydroxylupanine (503). Whereas we know a few parameters of olfactory qualities in Homo sapiens, often much less or hardly anything is known for most other vertebrates. 

Figure 7.10 Structures of the quinolizidine alkaloids, lupinine (21), lupanine (22), cytisine (23) and multiflorine (24) and of a dipiperidine alkaloid of the ammodendrine type (25).

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