Quinolizidines alkaloids

The synthetic utility of radical cyclization was used as the key step in a four-step synthesis of the natural product (d,0-epilupinine (134b, a quinolizidine alkaloid) (75CB1043) from methyl nicotinate (146). Thus, l-(4-bromobutyl)-3-methoxycarbonyl-l,4,5,6-tetrahydropyridine (140), obtained from methyl nicotinate (146), was cyclized to 141 (43%), which on reduction with LiAlH4 in THF provided 134b in 95% yield (89T5269). 

Racemic and chiral syntheses of some indolo[2,3-<2]quinolizidine alkaloids through a lactim ether route 98H(47)525. 

Molecular mechanics (MM) calculations have been employed for determining dihedral angles and to establish a comparison with values calculated from coupling constants, during conformational studies of tricyclic and tetracyclic quinolizidine alkaloids. The MM results had to be treated with care, as they sometimes predicted ring conformations different to those supported by experimental data <1999JST215>. 

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). 

Mass spectral data have also been employed for biological studies aimed at determining the distribution of quinolizidine alkaloids within a plant. For instance, the analysis of stem sections of Lupinus polyphyllus and Cytisus scoparius by laser desorption mass spectrometry led to the conclusion that these alkaloids are restricted to the epidermis and probably also to the neighboring one or two subepidermal cell layers <1984MI230>. 

Two-dimensional thin-layer chromatography (TLC) with adsorbent gradient has allowed the separation of quinolizidine alkaloids in the herb and in several alkaloids from Genista sp. <2004MI89>. 

Quinolizine alkaloids, including sophocarpine, matrine and sophoridine have been determined by GC-MS techniques in kuhuang, a traditional Chinese medicine (GC = gas chromatography) <2005MI967>. Similarly, GC-MS has allowed a phytochemical study of the quinolizidine alkaloids of Genista tenera <2005MI264>. 

The high-performance liquid chromatography (HPLC) determination of quinolizidine alkaloids in Radix Sophora flavescens was assisted by using tris(2,2 -bipyridyl)ruthenium(n) electrochemoluminescence <2004MI237>. Tandem HPLC-MS techniques have allowed the development of a sensitive and specific method for the determination of sophocarpine, matrine, and sophoridine in rabbit plasma <2005MI1595>. 

In an approach to simple Nuphar quinolizidine alkaloids, the piperidine compound 213 was converted to compound 214 that underwent one-pot detosylation, conjugate reduction, and cyclization to produce the quinolizidin-4-one 215... 

The intramolecular Pummerer reaction has been applied to the synthesis of simple quinolizidine alkaloids like lupinine <2000JOC2368>, and also to arenoquinolizine alkaloids. Thus, the 2-(2-piperidyl)indole 284 was converted to indolo[2,3- ]quinolizidine 287 following a protocol that has as the key step the regioselective cyclization onto the indole 3-position of a thionium ion generated by Pummerer reaction from the appropriately substituted compound... 

Dipolarophiles D3. 1,3-Dipolar cycloadditions of suitably functionalized cyclic nitrones with terminal alkenes, which have potential leaving groups X at the end of the alkane chain -(CHo),- (D3), were successfully used for the synthesis of pyrrolozidine, indolizidine and quinolizidine alkaloids, such as (+ )-and (—)-lentiginosine, a potent amyloglucosidase inhibitor (Scheme 2.243) (742). Reductive cleavage of the N-0 bond in the cycloadduct is important for the subsequent cyclization to pyrrolozidines, indolizidines, and quinolizidines. 

A review has appeared regarding the infrared and nuclear magnetic resonance spectroscopic investigations of quinolizidine alkaloids (303). The connection between the C/D ring junction and the existence of Bohlmann bands in the IR spectra of indolo[2,3-a]quinolizidines has been reinvestigated and interpreted (304). 

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... 

Figure 2.5 Anag5rine, teratogenic quinolizidine alkaloid from Lupinus spp.

Carey, D.B. and Wink, M. (1994). Elevational variation of quinolizidine alkaloid contents in a lupine Lupinus argenteus) of the Rocky Mountains, J. Chem. EcoL, 20, 849-857. 

Keeler, R.F. 1989. Quinolizidine alkaloids in range and grain lupins, in Cheeke, P.R., Ed., Toxicants of plant origin, Vol. I Alkaloids, CRC Press, Boca Raton, pp. 133-168. 

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. 

Wink, M. and Carey, D.B. (1994). Variability of quinolizidine alkaloid profiles of Lupinus argenteus (Fabaceae) from North America, Biochem. Systematics EcoL, 22, 663-669. 

Wink, M., Meibner, C. and Witte, L. (1995). Patterns of quinolizidine alkaloids in 56 species of the genus Lupinus, Phytochemistry, 38, 139-153. 

Lopez et al. reported the isolation of three quinolizidine alkaloids such as lupanine (30), 13-a-hydroxylupanine (31), and 17-oxo-lupanine (32) from Lupinus perennis Wild, (family Fabaceae) all these three isolates were found to have potent activity in enhancing glucose-induced insulin release from isolated rat islet cells in a glucose concentration-dependent manner. While the synthetic compound 2-thionosparteine... 

Yuzo et al. isolated three new quinolizidine alkaloids, javaberine A (37), javaberine A hexa-acetate (38), and javaberine B hexa-acetate (38) from Talinum paniculatum Gaertner (family Portulacaceae) all these three compounds (37-39) were found to be potent inhibitors of TNF-a... 

Garcia Lopez PM, de la Mora PG Wysocka W, Maiztegui B, Alzugaray ME, Del Zotto H, Borelli MI. (2004) Quinolizidine alkaloids isolated from Lupinus species enhance insulin secretion. Eur J Pharmacol 504 139-142. 

Cytisine (30) Varenicline (31) Quinolizidine alkaloid Smoking cessation... 

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