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In the presence of sparteine 2,4,6‐triisopropylbenzoates were lithiated enantioselectively in order to generate chiral d1 reagents. Their reaction with α‐halo boronic esters, resembling chiral a1 reagents, was explored. Enantiomerically enriched α‐halo boronic esters are readily available by Matteson Homologation (MH). A model reaction with α‐bromopentyl pinandiol boronate was optimized to an acceptable yield but proved to be quite sensitive. Generation of the d1 reagent from the corresponding stannane stabilized the protocol and delivered moderate yields for β‐unsubstituted α‐halo boronic esters. Good to excellent yields were obtained for β‐substituted α‐halo boronic esters, which can be generated by iterative MH, thus establishing this method as a useful terminus for an iterative Matteson sequence. [ABSTRACT FROM AUTHOR]

Allylic alcohols are a privileged motif in natural product synthesis and new methods that access them in a stereoselective fashion are highly sought after. Toward this goal, we found that chiral acetonide‐protected polyketide fragments performing the Hoppe–Matteson–Aggarwal rearrangement in the absence of sparteine with high yields and diastereoselectivities rendering this protocol a highly valuable alternative to the Nozaki–Hiyama–Takai–Kishi reaction. Various stereodyads and ‐triads were investigated to determine their substrate induction. The mostly strong inherent stereoinduction was attributed to a combination of steric and electronic effects. [ABSTRACT FROM AUTHOR]

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological purposes, were presently tested for antiarrhythmic, and other cardiovascular effects on isolated guinea pig heart tissues in comparison to well-established reference drugs. According to their structures, the tested compounds are assembled into three subsets: (a) N-(quinolizidinyl-alkyl)-benzamides; (b) 2-(benzotriazol-2-yl)methyl-1-(quinolizidinyl)alkyl-benzimidazoles; (c) N-substituted cytisines. All compounds but two displayed antiarrhythmic activity that was potent for compounds 4, 1, 6, and 5 (in ascending order). The last compound (N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase in the threshold of ac-arrhythmia. The tested compounds shared strong negative inotropic activity; however, this does not compromise the value of their antiarrhythmic action. On the other hand, only moderate or modest negative chronotropic and vasorelaxant activities were commonly observed. Compound 5, which has high antiarrhythmic potency, a favorable cardiovascular profile, and is devoid of antihypertensive activity in spontaneously hypertensive rats, represents a lead worthy of further investigation. [ABSTRACT FROM AUTHOR]

Highly enantiomerically enriched dihydrohydroquinolines were prepared in two steps from quinoline. Addition of aryllithiums to quinoline with tert‐butoxycarbonyl (Boc) protection gave N‐Boc‐2‐aryl‐1,2‐dihydroquinolines. These were treated with n‐butyllithium and electrophilic trapping occurred exclusively at C‐4 of the dihydroquinoline, a result supported by DFT studies. Variable temperature NMR spectroscopy gave kinetic data for the barrier to rotation of the carbonyl group (ΔG≠≈49 kJ mol−1, 195 K). Lithiation using the diamine sparteine allowed kinetic resolutions with high enantioselectivities (enantiomer ratio up to 99 : 1). The enantioenriched 1,2‐dihydroquinolines could be converted to 1,4‐dihydroquinolines with retention of stereochemistry. Further functionalisation led to trisubstituted products. Reduction provided enantioenriched tetrahydroquinolines, whereas acid‐promoted removal of Boc led to quinolines, and this was applied to a synthesis of the antimalarial compound M5717. [ABSTRACT FROM AUTHOR]

The Genisteae tribe belongs to the Fabaceae family. The wide occurrence of secondary metabolites, explicitly highlighting the quinolizidine alkaloids (QAs), characterizes this tribe. In the present study, twenty QAs (1–20), including lupanine (1–7), sparteine (8–10), lupanine (11), cytisine and tetrahydrocytisine (12–17), and matrine (18–20)-type QAs were extracted and isolated from leaves of three species (i.e., Lupinus polyphyllus ('rusell' hybrid), Lupinus mutabilis, and Genista monspessulana) belonging to the Genisteae tribe. These plant sources were propagated under greenhouse conditions. The isolated compounds were elucidated by analyzing their spectroscopical data (MS, NMR). The antifungal effect on the mycelial growth of Fusarium oxysporum (Fox) of each isolated QA was then evaluated through the amended medium assay. The best antifungal activity was found to be for compounds 8 (IC50 = 16.5 µM), 9 (IC50 = 7.2 µM), 12 (IC50 = 11.3 µM), and 18 (IC50 = 12.3 µM). The inhibitory data suggest that some QAs could efficiently inhibit Fox mycelium growth depending on particular structural requirements deduced from structure–activity relationship scrutinies. The identified quinolizidine-related moieties can be involved in lead structures to develop further antifungal bioactives against Fox. [ABSTRACT FROM AUTHOR]

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological purposes, were presently tested for antiarrhythmic, and other cardiovascular effects on isolated guinea pig heart tissues in comparison to well-established reference drugs. According to their structures, the tested compounds are assembled into three subsets: (a) N-(quinolizidinyl-alkyl)-benzamides; (b) 2-(benzotriazol-2-yl)methyl-1-(quinolizidinyl)alkyl-benzimidazoles; (c) N-substituted cytisines. All compounds but two displayed antiarrhythmic activity that was potent for compounds 4, 1, 6, and 5 (in ascending order). The last compound (N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase in the threshold of ac-arrhythmia. The tested compounds shared strong negative inotropic activity; however, this does not compromise the value of their antiarrhythmic action. On the other hand, only moderate or modest negative chronotropic and vasorelaxant activities were commonly observed. Compound 5, which has high antiarrhythmic potency, a favorable cardiovascular profile, and is devoid of antihypertensive activity in spontaneously hypertensive rats, represents a lead worthy of further investigation.

Anagyris foetida is a genus of legumes belonging to the Fabaceae family, considered as a good source of medications to treat various ailments. In order to determine the biological potential of this plant, the present work deals for the first time with the extraction and identification of alkaloids from leaves, stems and seeds of Algerian A. foetida species and evaluation of their antioxidant effects. The extraction was performed by three different methods to compare the influence of many factors (extraction temperature, nature and polarity of solvents) on the yield and chemical composition of extracts. Capillary GC-MS analyses of the obtained fractions allowed the identification of six alkaloids in the leaves and stems and five in the seeds, with a significant difference in the percentage content of identified compounds. The identified alkaloids include sparteine, N-methylcytisine, cytisine, 5,6-dehydrolupanine, lupanine and anagyrine. In vitro antioxidant activity of the alkaloids extracts was assessed by DPPH free radical scavenging test. Results showed that different parts of A. foetida exhibited relatively moderate scavenging of DPPH radicals. Extracts obtained by method III presented the highest antioxidant activity with IC50 = 108.7 ± 9.0 μg/mL for the leaves and stems and 92.9 ± 6.2 μg/mL for the seeds. These results suggested that cytisine, which was extracted only by method III in both samples, presented the highest antiradical activity. [ABSTRACT FROM AUTHOR]

Lupinus plants are well-recognized due to their significant alkaloid content, which has made them the subject of several studies. However, the lack of chemical and biological information on the Colombian Lupinus species remains a fact. Therefore, the alkaloidal fractions from the leaves of L. mirabilis obtained by conventional solvent and ultrasound-assisted extraction (CSE and UAE, respectively) at different time frames were analyzed. Sparteine (2) was the main component in all cases; however, its relative abundance showed large variability, ranging from 64.7% to 80.6%. Minor constituents were also affected by the extraction conditions. In general, prolonged times gave a higher proportion of alkaloids under CSE, while only a slight decrease was observed under UAE. Both the method and extraction time appeared to equally affect the ratios of particular alkaloids, leading to variations in their effect on the mycelial growth of Fusarium oxysporum. Holistic analysis through multiple-covariate statistical methods as an approach to integrating chemical and bioactivity datasets allowed inferring the compounds most likely responsible for the changes in mycelial growth inhibition. 13α-Hydroxylupanine (12) might represent a promising compound to be included in further studies against this phytopathogen. [ABSTRACT FROM AUTHOR]

Lupins are a promising source of protein that can complement soybean-based proteins in food and animal feed. Narrow-leafed lupin (Lupinus angustifolius) is the predominant lupin species cultivated in Australia and Europe. Consumption of lupin products can lead to toxicity in both humans and animals, primarily due to the presence of naturally occurring alkaloid compounds. The aim of the present research was to examine the alkaloid content of commercial narrow-leafed lupin grown in Australia and compare this to wild accessions. Nineteen accessions of narrow-leafed lupin were grown in a growth chamber with a day/night cycle of 18 h of light and 6 h of darkness. An LC-MS/MS-based method was deployed to detect and quantify the main alkaloids in lupins: angustifoline, 13α-hydroxylupanine, (+) lupanine, sparteine, (-) lupinine, isolupanine, and gramine. The alkaloid content in narrow-leafed lupin exhibited a wide variation among different genotypes. Sweet varieties such as Geebung had remarkably low alkaloid content, below 10 mg/kg. Bitter accessions such as P22660 displayed considerably higher alkaloid levels, as high as 20,000 mg/kg. The level of variation of alkaloids observed within lupin grain from different plant replicates of the same cultivars was significantly greater in sweet phenotypes (SD > 100 %) compared to bitter cultivars (SD < 20 %). • Sweet lupin varieties showed low alkaloid levels with 'Geebung' lowest at 8 mg/kg. • Bitter narrow leaf lupin accessions have high alkaloid levels of 100,000 mg/kg. • Alkaloid content of sweet lupin accessions can exceed the industrial safety limits. [ABSTRACT FROM AUTHOR]

Narrow-leaved lupine (Lupinus аngustifolius L.) is a widely cultivated leguminous forage and green manure crop with a potential for human nutrition. However, the presence of secondary metabolites – alkaloids – in lupine seeds considerably affects the quality of raw produce, reducing its nutritive value; in addition, high concentrations of alkaloids are toxic to humans and animals. Therefore, plant breeders working with lupine need to gain knowledge about the variability of alkaloid content in seeds of different genotypes and search for the sources of their low concentrations in the crop’s gene pool. The collection of narrow-leaved lupine genetic resources held by the N.I. Vavilov Institute of Plant Genetic Resources (VIR) offers wide opportunities for such search by means of mass screening. For its part, largescale gene pool screening requires the selection of an optimal technique to measure alkaloid content in seeds, so that it would be easily reproducible and as little labor-, time- and fund-consuming as possible. The results of the search for such method are presented. Qualitative and quantitative indices were compared when target compounds had been extracted with multicomponent mixtures and individual reagents (chloroform, methanol, etc.) and the extracts analyzed using gas chromatography-mass spectrometry. High-performance liquid chromatography combined with mass spectrometry was also employed. Five major alkaloids were found to be present in all types of extracts: lupanine, 13-hydroxylupanine (dominant ones), angustifoline, sparteine, and isolupanine. The fullest extraction of alkaloids was observed when the extractant with an added alkaline agent was used (425 mg/100 g). The lowest level of extraction was registered with chloroform (216 mg/100 g). The significance of the differences was confirmed statistically.

Kinetic resolution provided a highly enantioselective method to access a range of 3-aryl-3,4-dihydro-2 H -1,4-benzoxazines using n -butyllithium and the chiral ligand sparteine. The enantioenrichment remained high on removing the tert -butoxycarbonyl (Boc) protecting group. The intermediate organolithium undergoes ring opening to an enamine. The kinetic resolution was extended to give enantiomerically enriched substituted 1,2,3,4-tetrahydroquinoxalines and was applied to the synthesis of an analogue of the antibiotic levofloxacin that was screened for its activity against the human pathogen Streptococcus pneumoniae. [ABSTRACT FROM AUTHOR]

Sparteine is an alkaloid with bacteriostatic activity on the genus Mycobacterium. The aim of this study was to evaluate the antimicrobial activity of sparteine on the growth of 4 ATCC strains of Mycobacterium tuberculosis (susceptible, resistant to isoniazid, resistant to rifampicin and multidrug-resistant) in vitro. Validation of bactericidal activity of sparteine sulfate was carried out through an adaptation of the Microscopic-Observation Drug-Susceptibility (MODS) method according to the guidelines of the Peruvian National Health Institute. The results demonstrate that at concentrations of 25; 50 and 100 Mm of sparteine sulfate, there is no development of colony-forming units in any of the 4 evaluated strains. Our results demonstrate the potential in vitro antimicrobial effect of sparteine on multidrug-resistant tuberculosis. [ABSTRACT FROM AUTHOR]

Kinetic resolution of 2‐arylindolines (2,3‐dihydroindoles) was achieved by treatment of their N‐tert‐butoxycarbonyl (Boc) derivatives with n‐butyllithium and sparteine in toluene at −78 °C followed by electrophilic quench. The unreacted starting materials together with the 2,2‐disubstituted products could be isolated with high enantiomer ratios. Variable temperature NMR spectroscopy showed that the rate of Boc rotation was fast (ΔG≠≈57 kJ/mol at 195 K). This was corroborated by DFT studies and by in situ ReactIR spectroscopy. The enantioenriched N‐Boc‐2‐arylindolines were converted to 2,2‐disubstituted products without significant loss in enantiopurity. Hence, either enantiomer of the 2,2‐disubstituted products could be obtained with high selectivity from the same enantiomer of the chiral ligand sparteine (one from the kinetic resolution and the other from subsequent lithiation‐trapping of the recovered starting material). Secondary amine products were prepared by removing the Boc group with acid to provide a way to access highly enantioenriched 2‐aryl and 2,2‐disubstituted indolines. [ABSTRACT FROM AUTHOR]

One mechanism of invasive species success is the production of allelopathic chemicals that negatively affect native competitors. A highly invasive shrub, Cytisus scoparius, impedes Douglas-fir tree establishment in clearcuts, even years after its removal. This impediment may be from the allelopathic alkaloids of C. scoparius that could indirectly hinder Douglas-fir by inhibiting their mutualistic ectomycorrhizal fungi (EMF). I extracted and quantified alkaloids from C. scoparius tissue for use in a laboratory bioassay. I then tested if and how these alkaloids affected EMF growth. In a second assay, I tested the effects of three concentrations of pure sparteine, the primary alkaloid in C. scoparius , on fungal growth. Sparteine was the only alkaloid recovered from the extraction which yielded 0.32 mg sparteine/g fresh weight, a lower concentration than previously reported values. Both the crude extract and pure sparteine significantly affected fungal growth, but only sparteine produced a species-specific response. Growth was inhibited by increasing sparteine concentrations, and most species were inhibited at 1.4 mM, the concentration found in C. scoparius. One common EMF, Wilcoxina mikolae, was unaffected by sparteine while others, like Suillus caerulescens and Cenococcum geophilum, were more sensitive and stopped growing entirely at 5 to 10 mM. These results suggest that the alkaloids of C. scoparius may seriously hinder EMF, and indirectly Douglas-fir, contributing to the competitive dominance of the invasive shrub.

In the twenty-first century, one of the central focus of polymer research in academia and industries is directed towards the design of environmentally-benign materials produced from reagents that have minimal deleterious effects on our environment. The aliphatic polyester PLA is one such example. Due to its biodegradable, biorenewable and biocompatible nature, PLA finds diverse applications, especially in the biomedical field. PLA is exclusively synthesized by the ring-opening polymerization of lactide (cyclic dimer of lactic acid) in the presence of a catalyst. The macrocycles and macrocyclic metal moieties can act as effective catalysts for the polymerization resulting in the formation of PLA with controlled tacticity and predetermined molecular weight. This review reports metal-based catalytic systems supported by porphyrin, calixarene and bispyrrolidine- salan as ancillary ligand and metal-free organocatalyst sparteine for the ROP of LA. The variation in catalytic activity, tacticity of PLA, and PLA's molecular weight distribution by substitutional changes in the catalyst framework have been discussed in detail. [ABSTRACT FROM AUTHOR]

CYP2D6 metabolizes 20–25% of all clinically used drugs and its complex genetic polymorphism is a major determinant of drug safety and efficacy. We investigated the basis for the functional difference between the two common alleles *2 (g.2851C>T + g.4181G>C, normal function) and *41 (additional intronic g.2989G>A, reduced function). A recently reported far‐distant enhancer polymorphism rs5758550A/G linked to *2 has been suggested to play a decisive role. Genotyping of two white cohorts confirmed strong linkage of rs5758550G to *2, whereas no influence was found on metabolic ratio of sparteine or hepatic expression. Genomic plasmid constructs carrying individual variants or combinations thereof were expressed in COS1 and Huh7 cells. Both g.2851C>T(R296C) and g.2989G>A reduced enzyme activity and protein levels similarly by ~ 50–65% compared to reference (*1), whereas the double variant had only ~ 20% activity. Although the unexpected loss of function caused by g.2851C>T was compensated by g.4181G>C (mimicking the EM‐phenotype of *2), the additional loss of function due to intronic g.2989G>A in the triple variant was not compensated (mimicking the IM‐phenotype of *41). We also confirmed increased erroneous splicing in carriers of g.2989G>A but not of g.2851C>T as a likely explanation for the impaired function of *41. In conclusion, our data demonstrate g.2989G>A as causal variant of impaired allele CYP2D6*41 whereas triple‐haplotypes have to be considered to explain the functional difference between *2 and *41. These data are important for genotyping strategies and clinical implementation of CYP2D6 pharmacogenetics. [ABSTRACT FROM AUTHOR]

Background and Purpose: The metabolic activity of cytochrome P450 (CYP) 2D6 is highly variable and CYP2D6 genotypes insufficiently explain the extensive and intermediate metabolic phenotypes, limiting the prediction of drug response plus adverse drug reactions. Since CYP2D6 prototypic substrates are positively charged, the aim of this study was to evaluate the organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) as potential contributors to the variability of CYP2D6 hydroxylation of debrisoquine, dextromethorphan, diphenhydramine, perhexiline and sparteine. Experimental Approach OCT1/SLC22A1‐, OCT2/SLC22A2‐, OCT3/SLC22A3‐, MATE1/SLC47A1‐, and MATE2K/SLC47A2‐overexpressing cell lines were used to investigate the transport of the selected drugs. Individuals from a study cohort, well defined with respect to CYP2D6 genotype and sparteine pharmacokinetics, were genotyped for the common OCT1 variants rs12208357 (OCT1‐R61C), rs34130495 (OCT1‐G401S), rs202220802 (OCT1‐Met420del), rs34059508 (OCT1‐G465R), OCT2 variant rs316019 (OCT2‐A270S) and MATE1 variant rs2289669. Sparteine pharmacokinetics was stratified according to CYP2D6 and OCT1, OCT2 or MATE1 genotype. Key Results: OCTs and MATE1 transport sparteine and debrisoquine with high affinity in vitro, but OCT‐ and MATE1‐dependent transport of dextromethorphan, diphenhydramine and perhexiline was not detected. Sparteine and debrisoquine transport depends on OCT1 genotype; however, sparteine pharmacokinetics is independent from OCT1 genotype. Conclusions and Implications: Some drugs that are substrates of CYP2D6 are also substrates of OCTs and MATE1, suggesting overlapping specificities. Variability in sparteine hydroxylation in extensive and intermediate metabolizers cannot be explained by OCT1 genetic variants indicating presence of other factors. Dose‐dependent toxicities of dextromethorphan, diphenhydramine and perhexiline appear to be independent from OCTs and MATEs. [ABSTRACT FROM AUTHOR]

The [3,7]‐diazabicyclo[3.3.1]nonane (bispidine) structure is found in several interesting naturally occurring alkaloids. The most representative components are the tetracyclic alkaloid (−)‐sparteine and the tricyclic (−)‐cytisine alkaloids. Their biological activities have been known for a long time. In the literature, different syntheses of both tetracyclic and tricyclic structures have been reported, especially in the last few years, when a number of new reports renewed the interest in these fascinating molecules. Bicyclic bispidine derivatives have been thoroughly investigated in recent times also for their applications as catalysts, metal chelating agents, and lately in coordination polymers chemistry. In this review, we describe the most relevant strategies for the synthesis of molecules based on the [3,7]‐diazabicyclo[3.3.1]nonane core, related to (−)‐sparteine and (−)‐cytisine alkaloids. [ABSTRACT FROM AUTHOR]

This study aims to investigate the chemical constituents of the stem of Retama raetam growing in Saudi Arabia. The organic and inorganic composition of ethanol extract of R. raetam stem has been explored using direct analysis in real time-mass spectrometry (DART-MS), gas chromatography-mass spectrometry (GC-MS), and inductively coupled plasma-mass spectrometry (ICP-MS). Analysis conducted by DART-MS and GC-MS reveals the presence of several interesting organic constituents identified as 2,4-di-tert-butylphenol, sparteine, benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, methyl ester, phthalic acid, 1-octadecanol, squalene, argentamin, 2,4-di-tert-butylphenol, sparteine, benzene propanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, methyl ester, phthalic acid, 1-octadecanol, squalene, argentamin, and hentriacontane in the ethanol extract of the R. raetam stem. The ICP-MS analysis of stem extract showed the presence of a significant amount of important inorganic elements including aluminum, chlorine, calcium, bromine magnesium, phosphorus, scandium, and chromium. The current study complements other R. raetam extract investigations carried out in the past and provides the additional data for the future research studies. [ABSTRACT FROM AUTHOR]

Abstract The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids (QAs) in feed and food. This risk assessment is limited to QAs occurring in Lupinus species/varieties relevant for animal and human consumption in Europe (i.e. Lupinus albus L., Lupinus angustifolius L., Lupinus luteus L. and Lupinus mutabilis Sweet). Information on the toxicity of QAs in animals and humans is limited. Following acute exposure to sparteine (reference compound), anticholinergic effects and changes in cardiac electric conductivity are considered to be critical for human hazard characterisation. The CONTAM Panel used a margin of exposure (MOE) approach identifying a lowest single oral effective dose of 0.16 mg sparteine/kg body weight as reference point to characterise the risk following acute exposure. No reference point could be identified to characterise the risk of chronic exposure. Because of similar modes of action for QAs, the CONTAM Panel used a group approach assuming dose additivity. For food, the highest mean concentration of Total QAs (TotQAs) (i.e. the 6 most abundant QAs) was found in lupin seed samples classified as ‘Lupins (dry) and similar‐’. Due to the limited data on occurrence and consumption, dietary exposure was calculated for some specific scenarios and no full human health risk characterisation was possible. The calculated margin of exposures (MOEs) may indicate a risk for some consumers. For example, when lupin seeds are consumed without a debittering step, or as debittered lupin seeds high in QA content and when ‘lupin‐based meat imitates’ are consumed. For horses, companion and farm animals, other than salmonids, the available database on adverse effects was too limited to identify no‐observed‐adverse‐effect levels and/or lowest‐observed‐adverse‐effect levels and no risk characterisation was possible. For salmonids, the CONTAM Panel considers the risk for adverse effects to be low.

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Abnormal synchronous activity in neurons generates epileptic seizures. Antiepileptic drugs (AEDs) are effective in 70% of patients, but this percentage is drastically lower in developing countries. Sparteine is a quinolizidine alkaloid synthesized from most Lupine species and has a probable anticonvulsive effect. For this reason, the objective of the present work was to study the anticonvulsant effect of sparteine using a dose–effect curve and to determine its effectiveness against seizures using behavioral, electroencephalographic, morphological and molecular data. Wistar rats were grouped into control [saline solution (0.9%), pentylenetetrazole (90 mg/kg), and sparteine (13, 20 and 30 mg/kg), intraperitoneal (i.p.)] and experimental (sparteine + pentylenetetrazole) groups. The rats were implanted with surface electrodes to register electrical activity, and convulsive behavior was evaluated according to Velisek's scale. The rats were perfused to obtain brain slices for cresyl violet staining and cellular density quantification as well as for immunohistochemistry for NeuN and GFAP. Other animals were used to determine the hippocampal mRNA expression of the M2 and M4 acetylcholine receptors by qPCR. Sparteine exhibited a better anticonvulsant effect at a dose of 30 mg/kg (i.p.) than at the other doses used. This anticonvulsant effect was characterized by a decrease in the severity of convulsive behavior, 100% survival, an inhibitory effect on epileptiform activity 75 min after pentylenetetrazole administration, and the conservation of the cellular layers of CA1, CA3 and the dentate gyrus (DG); however, astrogliosis was observed after 30 mg/kg sparteine treatment. In addition, sparteine treatment increased the mRNA expression of the M4 receptor three hours after administration. According to our findings, the effective dose of sparteine as an anticonvulsant agent by i.p. injection is 30 mg/kg. The astrogliosis that was observed after sparteine administration may be a compensatory mechanism to diminish excitability and maintain neuronal homeostasis, possibly through redistributing potassium and glutamate. The increase in the mRNA expression of the M4 receptor may suggest the participation of the M4 receptor in the anticonvulsive effect of sparteine, as the activation of this receptor may inhibit acetylcholine release and facilitate the subsequent release of GABA. However, the precise mechanisms by which sparteine produces these effects are not known, and therefore, further experiments are necessary. [ABSTRACT FROM AUTHOR]

Products of lupin, a leguminous plant belonging to genus Lupinus, have high protein contents and are consumed in Mediterranean and Middle East countries. However, quinolizidine alkaloids (QAs) present in lupin have been reported to be toxic for humans and animals. Therefore, we carried out a quantitative determination of the QAs such as sparteine, angustifoline, lupanine, and 13-hydroxylupanine, which are known to be the major components in lupin and lupin products. The QAs were determined in three lupin products, namely, lupin beans, lupin cookies, and a lupin drink. The analysis was carried out using gas chromatography with a flame ionization detector (GC-FID) and the method was also validated. All of the QAs were eluted in 20 min, and the correlation coefficients were acceptable (R2 > 0.99). The limit of quantification in this method was lower than for a previously used capillary electrophoresis–mass spectrometric method. The total QA contents in lupin beans, lupin cookies, and lupin drink were 97.031, 4.786, and 67.887 µg/mL. Based on our results, it was concluded that these products were safe for consumption. It is believed that this method can be effectively used for the determination of QAs as GC-FID is a widely used technique. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anticancer effects of sparteine against human cervical cancer. Methods: Cell viability was determined by CCK8 assay, while 4′, 6-diamidino-2-phenylindole (DAPI) staining was used for determination of apoptosis. Cell cycle analysis was done with flow cytometry, while cell invasion was monitored using Transwell invasion assays. Protein expressions were determined using Western blotting. Results: The results revealed that sparteine inhibited the viability of cervical cancer cells with half-maximal inhibitory concentration (IC50) ranging from 10 to 25 µM. Sparteine exerted more profound antiproliferative effects on DoTc2 cells, with IC50 of 10 µM. However, minimal cytotoxicity was observed in normal cervical cells, as evident from the IC50 of 80 µM. Sparteine triggered the generation of ROS and apoptotic cell death in DoTc2 cells. The induction of apoptosis was accompanied by upregulation of Bax expression and downregulation of Bcl-2 expression. Sparteine caused arrest of DoTc2 cells at the G0/G1 phase of the cell cycle, and suppressed the expressions of cyclin A and cyclin B1. Transwell assay data showed that sparteine decreased the invasion ability of DoTc2 cells. Sparteine also inhibited the phosphorylation of VGFR2 in a concentration-dependent manner. Conclusion: Sparteine exhibits significant anticancer activity and may prove beneficial in cervical cancer chemotherapy. [ABSTRACT FROM AUTHOR]

The well‐established Hoppe–Beak chemistry, which involves enantioselective generation of organolithium compounds in the presence of (−)‐sparteine, was revisited and applied to unprecedented acylations with Weinreb amides to access highly enantioenriched α‐oxyketones and cyclic α‐aminoketones. Recycling of the sustainable solvent cyclopentyl methyl ether, sparteine, and the released Weinreb "amine" [HNMe(OMe)] was possible through a simple work‐up procedure that enabled full recovery of these precious materials. The methodology features a robust scope and flexibility, thus allowing the enantioselective preparation of scaffolds amenable of further derivatization. Well‐established Hoppe–Beak chemistry, which involves enantioselective generation of organolithium compounds in the presence of (−)‐sparteine, is revisited and applied to unprecedented acylations with Weinreb amides to access highly enantioenriched α‐oxyketones and cyclic α‐aminoketones. Recycling of the sustainable solvent cyclopentyl methyl ether, sparteine, and the released Weinreb "amine" [HNMe(OMe)] is possible through a simple work‐up procedure. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A protocol was developed for detecting and quantifying scopolamine, L-hyoscyamine, and sparteine. • Target analytes were extracted from animal-based food using EN-QuEChERS and analyzed by LC-MS/MS. • EDTA solution was employed to improve recovery. • LOQ values of 1–5 µg/kg were obtained for all analytes. Abstract We developed a modified Quick, Easy, Cheap, Effective, Rugged, and Safe (CEN QuEChERS) extraction method coupled with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI+/MS-MS) to identify and quantify residues of three botanical alkaloids, namely, scopolamine, L-hyoscyamine, and sparteine, in animal-derived foods, including porcine muscle, egg, and milk. A combination of ethylenediaminetetraacetic acid disodium buffer and acetonitrile acidified with 0.5% trifluoroacetic acid was used as an extraction solvent, whereas QuEChERS (CEN, 15662) kits and sorbents were applied for cleanup procedures. The proposed method was validated by determining the limits of quantification (LOQs), with values of 1–5 µg/kg achieved for the target analytes in various matrices. Linearity was estimated from matrix-matched calibration curves constructed using six concentration levels ranging from 1- to 6-fold increases in the LOQs of each analyte, and the correlation coefficients (R2) were ≥0.9869. Recoveries (at three concentration levels of 1-, 2-, and 3-fold increases in the LOQ) of 73–104% were achieved with relative standard deviations (RSDs) ≤7.7% (intra-day and inter-day precision). Ten types of each matrix procured from large markets were evaluated, and all tested samples showed negative results. The current protocol is simple and versatile and can be used for routine detection of plant alkaloids in animal food products. [ABSTRACT FROM AUTHOR]

Currently, there are many different methods of quantitative determination of alkaloid Sparteine amounts such as gravimetry, acidimetry, argentometry (including the use of ion-selective electrode), iodometry, extraction photometry, colorimetry, amperometry, potentiometry, direct ionometry with ion-selective electrode, thin layer chromatography, high-performance liquid chromatography and high pressure gas chromatography, also infrared and Nuclear magnetic resonance spectroscopy, chromatography-mass-spectrometry. It has been analyzed that most of the well-known methods are too insensitive, indiscriminate or too expensive, time-consuming and inaccessible. An application for analysis of amperometric titration techniques using both analytical reagent heteropolianions (GPA) Kehhina structure - standard solution 12-molibdophosphoric heteropolyacid and method of direct potentiometric determination using ISE for determining the choice amounts or amounts of alkaloids qinolizidine series in extracts are very promising, relatively simple in execution, express and sufficiently sensitive.

Graphical abstract Highlights • Arylsparteine derivatives are developed as potential antiproliferative agents. • Aryl substituents with electron withdrawing groups enhance antiproliferative potency. • Compound 10 blocks autophagic flux in cancer cells. • Compound 10 is more potent than 5-fluorouracil against A549 and U87 MG cancer cell lines. Abstract New series of arylsparteine derivatives were synthesized and evaluated for their cytotoxic activity against four human cancer cell lines (cervical epithelial carcinoma cells Hela, breast cancer cells MCF-7, lung cancer cells A549, and glioma cells U87 MG) and one normal fibroblast cell line. Structure-activity relationship revealed that introduction of 4-quinolinyl moiety to sparteine afforded a hybrid compound 10 with considerable antiproliferative activity against all tested cancer cell lines. Compound 10 , the most active agent in this study possessed IC 50 values of 5.97 ± 1.1 and 9.52 ± 0.3 μM against A549 and Hela cancer cell lines, respectively. Inhibition of autophagic flux proved to be the underlying mechanism for the antiproliferative activity of 10 which was further validated by decreased levels of ATP in cancer cells treated with 10. In addition, co-treatment of 10 and rapamycin restored cell viability which comes in good agreement with the proposed autophagic flux inhibition for 10. [ABSTRACT FROM AUTHOR]

An 8-step, gram-scale synthesis of the (−)-sparteine surrogate (22 % yield, with just 3 chromatographic purifications) and a 10-step, gram-scale synthesis of (−)-sparteine (31 % yield) are reported. Both syntheses proceed with complete diastereocontrol and allow access to either antipode. Since the syntheses do not rely on natural product extraction, our work addresses long-term supply issues relating to these widely used chiral ligands. [ABSTRACT FROM AUTHOR]

The reaction of dichlorocadmium(II) and (-)-sparteine (sp) provides two products, [CdCl2(sp)]) (1) and (Hsp)3[Cd2Cl7] (2). The latter represents one of the rare known examples exhibiting an isolated Cd2Cl73−trianion. Both products are formed in the same reaction mixture and single crystals of one of the two products can be obtained selectively by crystallization depending on the co-solvent. The formation and structural characterization of (H2sp)[CdCl4] (3) is also reported, crystallizing with either dichloromethane (3a) or water (3b) as guest molecules. [ABSTRACT FROM PUBLISHER]

The synthesis of a new class of epoxide derivatives from prochiral vinylidene bisphosphonate (VBP) precursors is reported using hydrogen peroxide as the terminal oxidant. The reaction is carried out using; a series of possible organic activators having a basic character, with the best results being observed using quinine and sparteine. These activators not only provide from good to excellent epoxide yields with a large variety of VBPs, but also intereeting enantioselectivitier in the °7%-96% ee range, at least in the case of ihe Phi and m-MeO-Ph VBP derivatives, opening the way to a number of chirel anii-ostooporosis potentially active pharmaceutical ingredients:. [ABSTRACT FROM AUTHOR]

A general and highly enantioselective arylation of carbamates derived from primary alcohols was developed by combining Hoppe's sparteine-mediated asymmetric lithiation with Negishi cross-coupling. Coupled with Aggarwal's lithiation-borylation sequence, the current method provides a short and divergent access to a variety of enantioenriched secondary and tertiary benzylic alcohols. [ABSTRACT FROM AUTHOR]

Sparteine is one of the most toxic quinolizidine alkaloids found in leguminous plants. Several studies have demonstrated that sparteine affects the nervous system, blocking the nervous ganglion, producing antimuscarinic effects, depressing the central nervous system and causing neuronal necrosis. However, there are no reports identifying the areas of the brain that are sensitive to the toxic effects of this alkaloid. 32 adult Wistar rats were on study, sixteen were implanted with an intracerebral stainless steel cannula and randomly assigned to a control or experimental group (n = 8). Animals, control and experimental, received daily intraventricular (ICV) injections of a sparteine or a sterile water solution for five consecutive days. Additionally, two groups of animals (8 rats each) received daily intraperotineal injections (IP) of a sparteine or sterile water solution for five consecutive days. 72 h after the last dose, the animals were sacrificed, their brains removed, fixed and embedded in paraffin to obtain 10 μm tissue slices. Brain slices were stained with H&E and evaluated under a light microscope. The main brain structures sensitive to sparteine were the cerebral cortex (frontal, fronto-parietal and striate) olfactory and amygdaloid areas, the ventromedial hypothalamic nucleus, the Purkinje cells in the cerebellum, and the CA1, CA3 and dentate gyrus regions of the hippocampus. Administration of sparteine, via ICV or IP, caused neuronal necrosis in brain structures, mainly related with cholinergic pathways. [ABSTRACT FROM AUTHOR]

(−)-Sparteine has proven itself to be a highly efficient and versatile ligand. However, in recent years it has become difficult to source. In addition the (+)-enantiomer is also not readily available. Here we report a suite of chiral diamines as potential sparteine surrogates. Chiral trans -1,2-diaminocyclohexane is commercially available in both enantiomeric forms and the parent structure can be easily modified. New (and known) chiral diamines have been tested in the asymmetric silylation of N -Boc pyrrolidine, N -Boc piperidine, the α-alkylation of dimethylhydrazones and in the rearrangement of meso -epoxides. While none match the selectivity of the highly evolved natural product, there is certainly potential for this class of diamine ligands to perform in a diverse set of asymmetric transformations. [ABSTRACT FROM AUTHOR]

The title ionic compound, (C15H28N2)[ZnCl4]·H2O, is isostructural with the CuII analogue published previously [Lee et al. (2004). Bull. Korean Chem. Soc. 25, 823–828; Jasiewicz et al. (2006). J. Mol. Struct. 794, 311–319]. The [ZnCl4]2− anion is, however, much more close to the tetrahedral conformation than the [CuCl4]2− ion. In the tetrachloridozincate anion, the Cl—Zn—Cl angles are in the range 103.57 (3)–116.81 (3)°.

Sparteine N1-oxide and α-isosparteine N-oxide were prepared and theirstructures determined for the first time by 1H- and 13C-NMR spectroscopy using twodimensionaltechniques. The N-oxide effects were also calculated.

Sparteine is a quinolizidine alkaloid extracted from Lupinus that has numerous pharmacological properties both in humans and animal models. In the central nervous system, sparteine reduces locomotor activity, has light analgesic effects, also has no effects on short-term memory or spatial learning and does not induce changes in behavior or electroencephalographic (EEG) activity. However, the anticonvulsant profile of sparteine is not fully characterized in experimental animals and there are no data in humans. Therefore, the present review focuses on the experimental evidence supporting the anticonvulsant action of sparteine in models of acute seizures and status epilepticus (SE), as well as its possible mechanisms of action. The evidence that supports the anticonvulsant effect of (-)-Sparteine sulfate includes the inhibition of seizures induced by maximal electro-stimulation, a delay in the onset of convulsive behavior and the prolongation of survival time in mice treated with pentylenetetrazole (PTZ). Additionally, sparteine delays the onset of convulsive behavior and decreases the severity and mortality of rats treated with PTZ and pilocarpine. Sparteine decreases amplitude and frequency or blocks the epileptiform activity induced by PTZ, pilocarpine and kainic acid. Sparteine may decrease hyperexcitability through the activation of the M2 and M4 subtypes of mAChRs, which is a probable mechanism of action that together with its systemic effects may favor its anticonvulsant effects against seizures and SE. [ABSTRACT FROM AUTHOR]

Chiral carbon nanoparticles (CCNPs) were developed by surface passivation using the chiral ligand (−)-sparteine or (+)-sparteine (denoted (−)-SP/CNP and (+)-SP/CNP, respectively). The chirality of the prepared CCNPs was demonstrated by circular dichroism and polarimetry and employed as an enantioselective separation platform for representative racemic mixtures. [ABSTRACT FROM AUTHOR]

Three chiral derivatives of the alkaloid sparteine (bispidines), characterized by the 3,7-diazabicyclo[3.3.1]nonane moiety, were designed as efficient ligands in a number of due to their metal coordination properties. A full evaluation of the 3D properties of the compounds was carried out, as the geometrical features of the bicyclic framework are strictly related to the efficiency of the ligands in the . The selected molecules have different molecular complexity for investigating the effects of different chiral groups on the bicycle conformation. We report here a thorough analysis of their molecular arrangement, by NMR spectroscopy, single crystal X-ray crystallography, and computational techniques, which put in evidence their conformational preferences and the parameters needed for the design of more efficient ligands in asymmetric synthetic routes. The results confirmed the high molecular flexibility of the compounds, and indicated how to achieve a control of the chair-chair/boat-chair conformational ratio, by adjusting the relative size of the substituents on the piperidine nitrogens. Chirality 28:332-339, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A novel synthesis of quinolizidines by a cationic gold-catalyzed double cyclization cascade has been developed. The reaction was initiated by the gold-catalyzed 6- exo- dig cyclization of ynamides, which was followed by a second cyclization of an enamide intermediate to provide the corresponding quinolizidine derivatives. The utility of this reaction was demonstrated by application to the synthesis of multi-substituted quinolizidines and by the total synthesis of a quinolizidine alkaloid, (±)-lupinine. [ABSTRACT FROM AUTHOR]

The effect of organolithium reagent (RLi: R=nBu, iPr, sBu, tBu), solvent (diethyl ether, diethyl ether/THF and MTBE), and stoichiometry on the (–)-sparteine-mediated silylation of 7,8-dipropyltetrathia[7]helicene shows that, unusually, substantially more than 0.5 equivalent of RLi (R=iPr, sBu, tBu) and a large excess of (–)-sparteine (R=nBu, sBu) is often needed to achieve substantial conversions and good ee values. With nBuLi, however, just one equivalent of the organolithium reagent is sufficient to obtain high conversions. Our best results were obtained using the convenient tBuLi/(–)-sparteine adduct with which the need for a high (–)-sparteine/RLi ratio can be avoided. Single- and double-kinetic resolution (KR) procedures give enantiopure samples of 2- trimethylsilyl- and 2,13-di(trimethylsilyl)-7,8-dipropyltetrathia[ 7]helicene and two-step double-KR combining (–)-sparteine/sBuLi and chiral formamides affords the synthetically valuable 2-formyl-7,8-dipropyltetrathia[7]helicene. This is the first use of (–)-sparteine for the enantioselective lithiation of helicenes and the first report of tBuLi outperforming sBuLi in a (–)-sparteine-mediated procedure. [ABSTRACT FROM AUTHOR]

The synthesis of a new class of epoxide derivatives from prochiral vinylidene bisphosphonate (VBP) precursors is reported using hydrogen peroxide as the terminal oxidant. The reaction is carried out using a series of possible organic activators having a basic character, with the best results being observed using quinine and sparteine. These activators not only provide from good to excellent epoxide yields with a large variety of VBPs, but also interesting enantioselectivities in the 67%–96% ee range, at least in the case of the Ph and m-MeO–Ph VBP derivatives, opening the way to a number of chiral anti-osteoporosis potentially active pharmaceutical ingredients.

Quinolizidine alkaloids isolated from various marine and terrestrial animals and plants are primarily composed of lupinine-, matrine-, and sparteine-type alkaloids. Matrine, phenanthroquinolizidines, bis-quinolizidines, and small molecules from amphibian skins are representative compounds of such alkaloids. Quinolizidine alkaloids harbor anticancer, antibacterial, antiinflammatory, antifibrosis, antiviral, and anti-arrhythmia. In this chapter, we comprehensively outline the biological activity and pharmacological action of quinolizidine alkaloids and discuss new avenues toward the discovery of novel and more efficient drugs based on these naturally occurring compounds. It is urgent for basic research and clinical practice to conduct more targeted comprehensive research based on the lead drugs of quinolizidine alkaloids with significant pharmacological activity., Competing Interests: Conflict of interests All authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The long-term effects of status epilepticus (SE) include severe clinical conditions that result in disorders of various organs and systems as well as neurological damage that could lead to death. Sparteine is a quinolizidine alkaloid synthesized from most Lupine species, and its anticonvulsive effect was evaluated in the pentylenetetrazole model of SE. However, efforts to clearly determine the anticonvulsive effect of sparteine have not been made previously. For this reason, we consider it important to study the anticonvulsant effects of sparteine at the level of behavior and EEG activity in three different SE models. The animals of the control groups, which received intraperitoneal pentylenetetrazole (90 mg/kg), kainic acid (9 mg/kg) or pilocarpine (370 mg/kg), exhibited convulsive behavior and epileptiform activity. After sparteine pretreatment (13 mg/kg, administered 30 min before the convulsive drug), the animals administered pentylenetetrazole and pilocarpine exhibited reduced mortality rates compared with the corresponding control groups, while the animals administered kainic acid exhibited a delayed onset of convulsive behavior and decreased seizure duration compared with the corresponding control group. In the three models of SE, a significant reduction in the amplitude and frequency of discharge trains was observed. These results support the anticonvulsant effect of low doses of sparteine and allow us to direct our efforts to other new anticonvulsant strategies for seizure treatment. However, it is necessary to perform more experiments to determine the precise mechanism through which sparteine produces an anticonvulsant effect at this concentration. [ABSTRACT FROM AUTHOR]

The chemical composition of the lipophilic extracts of the stems and grains of the shrub Retama sphaerocarpa was investigated by gas chromatography–mass spectrometry for the first time. Fatty acids is the major family of compounds in both morphological parts, representing between 37.1 and 85.1% of the total compounds detected, followed by sterols in stems and monoglycerides in grains. Considerable amounts of the alkaloids retamine (9.6 g kg −1 of dry material) and cytisine (0.6 g kg −1 of dry material) were also found in stems and grains, respectively. Before alkaline hydrolysis octadec-9-enoic (0.7–2.4 g kg −1 of dry material), octadeca-9,12-dienoic (1.5–2.9 g kg −1 of dry material) and hexadecanoic (1.1–2.0 g kg −1 of dry material) acids are the most abundant lipophilic components in both morphological parts. After alkaline hydrolysis the contents of octade-9-enoic, octadeca-9,12-dienoic and octadeca-9,12,15-trienoic acids detected increased considerably ranging from 1.9 to 22.4, 3.6 to 40.1 and 0 to 8.6 g kg −1 of dry material, respectively. Smaller amounts of long-chain aliphatic alcohols, α-tocopherol and β-amyrin were also found. These data indicates that R. sphaerocarpa stems and grains are a potential source of valuable phytochemicals, with recognized nutritional and phytopharmaceutical applications. [ABSTRACT FROM AUTHOR]

The article focuses on asymmetric syntheses of 3,4-disubstituted tetrahydroquinoline derivatives using (+)-sparteine-mediated electrophilic substitution. Topics include the use of epoxide for electrophilic substitution and amino alcohol as the derivative, the use of diastereomeric mixtures, and stereoselective lithiation.

Two efficient protocols are described for the transformation of a key chiral homoallyllic sulfinamine intermediate in four steps into enantioenriched 7-methoxycryptopleurine. While one of the protocols relied on a rhodium catalyzed linear hydroformylation process, the alternative approach was based on a ring-closing metathesis from the corresponding N-allyl-sulfinamine. The cytotoxic evaluation of both enantiomers of the target compound demonstrated that the (R)-compound is much more potent than its antipode against the four cancer cell lines examined. [ABSTRACT FROM AUTHOR]

Four new copper(II)/diamine complexes comprising some (+)-sparteine surrogates and a cyclohexane-derived diamine were prepared and evaluated as chiral catalysts in desymmetrisation of meso -diols and asymmetric Henry reactions. Mono-benzoylation reactions generated two products with high enantioselectivity (90:10 to 97:3 er). Asymmetric Henry reactions gave nitro alcohols in 90:10 to 98:2 er. Notably, the sense of induction with the (+)-sparteine surrogates was opposite to that obtained using the copper(II)/(−)-sparteine complex. One of the nitro alcohol products was utilised in a concise synthesis of a chiral morpholine. [ABSTRACT FROM AUTHOR]

ABSTRACT Changes in vibrational circular dichroism (VCD) were recorded on-line during a chemical reaction. The chiral complex nickel-(-)-sparteine chloride was hydrolyzed to free (-)-sparteine base in a biphasic system of solution and chloroform (CHCl3). Infrared (IR) and VCD spectra were iteratively recorded after pumping a sample from the CHCl3 phase through a lab-built VCD spectrometer equipped with a tunable mid-IR quantum cascade laser light source, which allows for VCD measurements even in the presence of strongly absorbing backgrounds. Time-dependent VCD spectra were analyzed by singular value decomposition and global exponential fitting. Spectral features corresponding to the complex and free (-)-sparteine could be clearly identified in the fitted amplitude spectrum, which was associated with an exponential decay with an apparent time constant of 127 min ( t½ = 88 min). Chirality 26:130-136, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]