Erythrina Alkaloids Research Articles

Spokewise Total Syntheses of Four Erythrina Alkaloids and Telescoped Syntheses of Six Additional Alkaloids.

Based on rich sulfur-involving chemical transformations, a novel spokewise synthetic strategy, a subclass of the collective strategies, has been developed to concisely synthesize four erythrina alkaloids through a single-step transformation from a common synthetic precursor. Moreover, six additional erythrina alkaloids have also been synthesized by subsequent 1-2 steps chemical transformations. The current synthetic approaches provide a valuable platform for collective total syntheses of erythrina alkaloids and pseudo-natural erythrina alkaloids.

Phytochemical variation between hydrochloric and tartaric acid-derived alkaloidal extracts of Erythrina fusca Lour. leaves: A proton NMR-based approach

Erythrina fusca Lour. (Fabaceae) has been used traditionally to relieve toothache and migraine headaches, cleansing putrid ulcers, and reducing skin inflammations and irritation. Interestingly, most of the reported biological activities on the plant are attributed to its Erythrina alkaloids which are usually extracted through the acid-base method. While the selection of acids for the extraction process is crucial, there is limited information on comparing the efficacy of strong organic and inorganic acids in extracting Erythrina alkaloids, and, more broadly, other types of alkaloids. In this study, comparison between hydrochloric acid (HCl) and tartaric acid (H2T) was made to extract the Erythrina alkaloids. From the same mass (10 g) of the crude methanolic leaf extract, a significantly higher (9-fold) alkaloidal yield was obtained using H2T compared to the HCl. The alkaloidal extracts displayed different proton nuclear magnetic resonance (1H NMR) profile where identification of their phytochemical constituents was done extensively through comparison with respective data of previously isolated compounds from the Erythrina species. Forty-seven phytochemicals were identified in the HCl extract and they were mostly alkaloids. While the H2T extract not only contained alkaloids, but also flavonoids, and pterocarpans. Cumulatively, 83 phytochemicals were identified from the extracts, including 35 alkaloids, 18 flavonoids, 14 pterocarpans, 9 terpenes, 3 phenols, and 4 saponins. Based on multivariate analysis (MVDA), the alkaloids erysodine (1), erysovine (2), erysopine (3), warangalone (39), calopocarpin (53), and dolichin A (60) were found in both alkaloidal extracts. The PLS-DA model further identified the variation in the two extracts where the HCl extract was characterized by the flavonoids lupinifolin (41) and erythrisenegalone (43). Conversely, the H2T extract contained a broader range of phytochemicals, including the alkaloids glucoerysodine (21) and erythratidinone (28), the flavonoids 5,3′-dihydroxy-4′‑methoxy-5′-(3-methyl-1,3-butadienyl)-2′′,2′′dimethylpyrano-[5,6:6,7]-isoflavanone (51), 5,3′-dihydroxy-5′-(3‑hydroxy-3-methyl-1-butenyl)-4′‑methoxy-2′′,2′′dimethylpyrano-[5,6:6,7]-isoflavanone (52), and catechin (82), the pterocarpans calopocarpin (53) and sandwicensin (63), the terpenes loliolide (70), ursolic acid (80), propyloxyamyrin (83), and stigmast-3-en-4-one (73), the saponins sigmoisides A, B, and E (75, 76, and 77), and the phenol methyl gallate (81). The present findings highlight the value of targeting the extraction process for alkaloids, in this instance Erythrina alkaloids, using different type of acids. Furthermore, these compounds may be considered potential markers that were selectively extracted through the acid-base extraction process.

Total synthesis of (±)-3-demethoxyerythratidinone via Tf2O-promoted cascade reaction of enaminone.

The tetracyclic rings with chiral quaternary center represent a formidable synthetic challenge for Erythrina alkaloids. We present a 6-step synthesis of the Erythrina alkaloid 3-demethoxyerythratidinone with a 16% overall yield. Our synthesis highlights a cascade reaction initiated by Tf2O-induced activation of an enaminone substrate, yielding an iminium species and an enol triflate, followed by a Pictet-Spengler reaction. This method efficiently constructs the tetracyclic core skeleton, featuring an N-substituted quaternary center. It exhibits versatility across diverse (hetero)arenes and enaminone structures, providing a general strategy for the rapid synthesis of fused or spiro ring systems including the core structure of homoerythrina alkaloids.

Metabolomic study of the estrogenic and anti-osteoporotic potential of Erythrina bidwillii leaf.

Erythrina bidwillii Lindl., Leguminosae, constitutes a valuable crop for horticulture and medicine; however, it is rarely investigated. Menopause is a crucial transitional period in women's health. Women worldwide consider the use of phytoestrogens as a safe hormone replacement therapy to alleviate detrimental menopausal symptoms. Thus, the discovery of novel phytoestrogens is highly demanded. The present study aimed to investigate, for the first time, the metabolomic profile and the estrogenic potential of E. bidwillii Lindl. leaf. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and gas chromatography-mass spectrometry metabolite profiling revealed the prevalence of alkaloids, flavonoids, isoflavonoids and fatty acids. Additionally, five erythrinan alkaloids, cristanine A (1), 8-oxoerythraline (2), (+)-erythrinine (3), (+)-erythraline (4) and 8-oxoerythrinine (5), along with the isoflavonoid genistin (6), were isolated. Erythrina bidwillii leaf extract exhibited significant in vivo estrogenic, anti-osteoporotic, anti-hyperlipidemic, hepatoprotective, and nephroprotective activities, utilizing ovariectomized rat model. Moreover, ethyl acetate and hexane fractions possessed significant in vitro estrogeic potential on MCF-7 cell lines. An in silico study of the isolated metabolites revealed that (+)-erythrinine (3) and 8-oxoerythrinine (5) exhibited the highest affinity for ERα and ERβ, respectively, modeling them as potential estrogenic lead metabolites. Therefore, E. bidwillii leaf could be employed as promising hormone replacement therapy for postmenopausal women after thorough clinical trials.

Erythrina Alkaloids: An Updated Review with Neurological Perspective.

Erythrina Alkaloids: An Updated Review with Neurological Perspective.

Dimeric alkaloids from the barks of Erythrina variegata as well as their occurrence

Thirteen undescribed dimeric Erythrina alkaloids, named as erythrivarines A1–A13, were isolated from the barks of Erythrina variegata L. and. Their structures were determined on the basis of NMR, UV and mass spectral analyses. Dimeric Erythrina alkaloid with a C-8/8′ linkage in erythrivarine A1 was not yet reported. Representative dimers from titled plant were used to prove their occurrence as natural products by LC − MS detection. Additionally, simultaneous investigation enabled us to propose the natural property of seemingly artificial Erythrina alkaloid with acetonyl group.

Dimeric Erythrina alkaloids as well as their key units from Erythrina variegata

Ten dimeric and two monomeric Erythrina alkaloids, all of them are undescribed, were isolated from the bark of Erythrina variegata L. and named as erythrivarines O–Z. Their structures were determined on the basis of NMR and UV-spectroscopy and mass spectrometry. Dimeric Erythrina alkaloids with a C-10/11′ linkage in erythrivarine O and a C-7/10′ connectivity in erythrivarines P–U are not yet reported. The two identified monomeric alkaloids may be the precursors of the described dimeric derivatives. These co-occurring dimeric and monomeric alkaloids enabled us to propose a possible biosynthetic pathway leading to these dimers. Their effects of preventing hearing loss were additionally evaluated and erythrivarine T showed as a potential protector of the House Ear Institute-Organ of Corti 1 (HEI–OC–1) cells against neomycin.

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of <i>Erythrina</i> Alkaloids

Five new Erythrina alkaloids from the stems of Erythrina corallodendron

Five new Erythrina alkaloids and five known E. alkaloids were isolated from a 95% ethanol extract of the stems of Erythrina corallodendron L. Their chemical structures were elucidated by UV, IR, HRESIMS, NMR and X-ray. Furthermore, the analgesic activities of E. alkaloids 1, 2 and 6 were evaluated by using an acetic acid-induced writhing test in mice, and their writhing inhibition rates were 67.9%, 64.6% and 70.3% at doses of 20 mg/kg, respectively.

A stereospecific total synthesis of DL-hexahydroapoerysopine.

A stereospecific total synthesis of DL-hexahydroapoerysopine, an intriguing and historically important Apo rearrangement product of the aromatic Erythrina alkaloids bearing the all-cis ring fusion stereochemistry, was achieved via an efficient acid-mediated stereospecific skeletal rearrangement.

Three new erythrina alkaloids from the roots of Erythrina corallodendron

Three new erythrina alkaloids, eryalkals A (1), B (2), and C (3), were isolated from the roots of Erythrina corallodendron L. Their structures, including their absolute configurations, were elucidated based on analyses of HR-ESI-MS, 1D/2D NMR and single-crystal X-ray diffraction techniques. The isolated erythrina alkaloids were screened for the antioxidant and cytotoxic activities. All the compounds showed no antioxidant activity and cytotoxic activities.

Colored Dimeric Alkaloids from the Barks of Erythrina variegata and Their Neuroprotective Effects.

Five dimeric Erythrina alkaloids, named erythrivarines J-N, were isolated from the barks of Erythrina variegata L. (Fabaceae). The erythrivarines J-L featured a 6/6/5/6/6/5/6/6/6 ring system and super conjugated double bond systems, causing intense color from blue to wine red, while erythrivarines M-N looked orange. The structures of the isolated compounds were elucidated by 1D and 2D NMR experiments combined with MS and confirmed by the X-ray crystal diffraction technique. The performed bioassay using HEI-OC-1 cells revealed neuroprotective properties of erythrivarine N against the hearing loss causing antibiotics, neomycin.

Two Erythrina alkaloids and three diarylpropanoids from Erythrina velutina

Two new Erythrina alkaloid glycosides, 1 and 2, and three new diarylpropanoid glycosides 12–14 together with nine known compounds were isolated from the MeOH extracts of the seeds of Erythrina velutina. The structures and absolute configurations of these new compounds were elucidated through comprehensive spectroscopic analyses as well as experimental and calculated ECD data. The inhibitory potency of these compounds against nitric oxide production in LPS-induced RAW 264.7 cells and the cytotoxicity of these compounds against the HeLa and HL-60 human cancer cell lines were also discussed.

Erythrina alkaloids from stems of Erythrina corallodendron

This study aims to investigate Erythrina alkaloids from the stems of Erythrina corallodendron. Eighteen Erythrina alkaloids were isolated from the 95% ethanol extract of the stems of E. corallodendron by silica gel,octadecyl silica( ODS),Sephadex LH-20 column chromatography and preparative HPLC. With nuclear magnetic resonance( NMR) spectroscopy and mass spectrometry( MS),their structures were identified as crstanine A( 1),erytharbine( 2),cristamine C( 3),( +)-erystramindine( 4),10,11-dioxoerythraline( 5),8-oxoerythraline( 6),8-oxo-11β-methoxyerythradine( 7),11-methoxyerythradine( 8),( ±)-11-epi-methoxyerythraline( 9),( +)-erythraline( 10),crystamidine( 11),8-oxoerythrinine( 12),( +)-11α-hydroxyerysotrine( 13),erythrinine( 14),erysodine( 15),erysotrine-N-oxide( 16),( +)-erythratidine( 17),erythratine( 18). Compounds 1-4,7,9,11,13,16 and 17 were isolated from E. corallodendron for the first time. Furthermore,the cytotoxic activities of these Erythrina alkaloids were screened by MTT assay. The results showed that all compounds had no obvious cytotoxic activity. The analgesic activities of compounds1,6 and 8 were evaluated using an acetic acid-induced writhing test in mice. The writhing inhibition rates of compounds 1,6 and 8 at20 mg·kg~(-1)( ip) were 69%,70% and 62%,respectively( P&lt;0. 01),indicating they have significant analgesic activity.

Erythrina Alkaloid Analogues as nAChR Antagonists–A Flexible Platform for Leads in Drug Discovery

Erythrina alkaloids and their central nervous system effects have been studied for over a century, mainly due to their potent antagonistic actions at β2-containing nicotinic acetylcholine receptors (nAChRs). In the present work, we report a synthetic approach giving access to a diverse set of Erythrina natural product analogues and present the enantioselective total synthesis of (+)-Cocculine and (+)-Cocculidine, both found to be potent antagonists of the β2-containing nAChRs.

New Selective Human MAO-B Inhibitors from the Stems of Erythrina corallodendron L.

One new, 10, 11-dioxo-6,7α-erythraline epoxide (A1) and four known erythrinan alkaloids 10, 11-dioxo-erythraline (A2), erysodine (A3), 8-oxo-erythraline (A4) and erythraline (A5) were isolated from the 70% methanolic extract of stems of E. Corallodendron (Fabaceae). The isolated compounds were elucidated by exploiting 1D/2D NMR, and HR-ESI-MS analysis. The absolute configuration of A1 was determined by electronic circular dichroism (ECD). Mono Amine Oxidase inhibitory activity of the isolated alkaloids was investigated in vitro using kynuramine deamination assay on recombinant human MAO-A and B enzymes. The binding modes were predicted by molecular docking and the structure activity relationships of erythrinans were then evaluated. All isolated alkaloids demonstrated preferential activity against MAO-B. A1 displayed the highest potency and selectivity against MAO-B with IC50 of 25.18 μM, (SI &gt;3.97). The selective inhibition exhibited by erythrinan alkaloids against MAO-B is in line with the expected biological impact of Erythrina in the treatment of neurodegenerative diseases and presents this chemical class as promising leads for managing AD and PD diseases.

Erythrina velutina Willd. alkaloids: Piecing biosynthesis together from transcriptome analysis and metabolite profiling of seeds and leaves

IntroductionNatural products of pharmaceutical interest often do not reach the drug market due to the associated low yields and difficult extraction. Knowledge of biosynthetic pathways is a key element in the development of biotechnological strategies for plant specialized metabolite production. Erythrina species are mainly used as central nervous system depressants in folk medicine and are important sources of bioactive tetracyclic benzylisoquinoline alkaloids (BIAs), which can act on several pathology-related biological targets. ObjectivesIn this sense, in an unprecedented approach used with a non-model Fabaceae species grown in its unique arid natural habitat, a combined transcriptome and metabolome analyses (seeds and leaves) is presented. MethodsThe Next Generation Sequencing-based transcriptome (de novo RNA sequencing) was carried out in a NextSeq 500 platform. Regarding metabolite profiling, the High-resolution Liquid Chromatography was coupled to DAD and a micrOTOF-QII mass spectrometer by using electrospray ionization (ESI) and Time of Flight (TOF) analyzer. The tandem MS/MS data were processed and analyzed through Molecular Networking approach. ResultsThis detailed macro and micromolecular approach applied to seeds and leaves of E. velutina revealed 42 alkaloids, several of them unique. Based on the combined evidence, 24 gene candidates were put together in a putative pathway leading to the singular alkaloid diversity of this species. ConclusionOverall, these results could contribute by indicating potential biotechnological targets for modulation of erythrina alkaloids biosynthesis as well as improve molecular databases with omic data from a non-model medicinal plant, and reveal an interesting chemical diversity of Erythrina BIA harvested in Caatinga.

Pharmacological characterisation of anticonvulsant effects elicited by erythrartine.

The erythrinan alkaloids erythravine and 11α-hydroxy-erythravine from Erythrina verna (Vell.) have been extensively investigated for their anxiolytic and anticonvulsant effects. Both are structurally similar to the erythrartine that also exhibit anxiolytic effects, but there is no report on its anticonvulsant potential. Since some anxiolytic drugs can be useful in the management of epileptic seizures, we investigated whether erythrartine could prevent seizures induced by different chemoconvulsants. Experiments were performed using different concentrations of erythrartine injected via intracerebroventricular in rats submitted to pilocarpine, kainic acid, pentylenetetrazol or picrotoxin-induced seizures. Moreover, the rotarod test was performed to verify the effects of erythrartine on animal motor coordination. Our data showed for the first time that erythrartine prevented the occurrence of seizures induced by all of the chemoconvulsants tested and did not affect locomotor performance neither produced sedative effect on animals. Obtained results validate the ethnopharmacological significance of E. verna and provide new information on erythrartine, another erythrinian alkaloid of biotechnological and medicinal interest.

Tandem Reaction of Tertiary Enamides as a Synthetic Strategy to Construct the Fused N-Pentacyclic Skeleton of Erythrina Alkaloid Derivatives.

An exquisite protocol to the synthesis of erythrina-related structural derivatives was developed, which is composed of a nucleophilic addition of tertiary enamides to ketonic carbonyls and the trapping of acyliminium by an aromatic unit. This protocol afforded a powerful method for the construction of diverse fused N-pentacyclic skeletons in high efficiency and excellent diastereoselectivity by just using different acid catalysts.

Construction of the Erythrinane Core Skeleton via Asymmetric Catalytic Cascade Reaction of Tertiary Enamides.

We report herein an efficient cascade strategy for the rapid construction of a highly enantioenriched erythrinane core skeleton. Under the sequential catalysis of a chiral Cr(III)(salen)Cl and InCl3, cyclohexanone-derived tertiary enamides undergo an intramolecular enantioselective nucleophilic addition followed by diastereoselective Pictet-Spengler cyclization. This method is highly enantio- and diastereoselective, leading to diverse erythrina alkaloid derivatives as the sole diastereoisomer with up to 98% ee.