Erythrina Alkaloids Research Articles

Pd‐Catalyzed Asymmetric Intramolecular Arylative Dearomatization of para‐Aminophenols†

Summary of main observation and conclusionAsymmetric arylative dearomatization reactions of para‐aminophenols are realized by a Pd‐catalyst consisting of a TADDOL (α,α,α',α'‐tetraaryl‐2,2‐disubstituted 1,3‐dioxolane‐4,5‐dimethanol)‐derived chiral phosphoramidite ligand. The tetracyclic products bearing the key skeleton of Erythrina alkaloids are afforded in reasonable yields (up to 73%) with good to excellent enantioselectivity (up to 97% ee). Concise total synthesis of (–)‐3‐demethoxyerythratidinone is achieved by employing this method as the key step.

Artificial Erythrina Alkaloids from Three Erythrina Plants, E. variegata, E. crista-galli and E. arborescens

Fourteen unprecedented artificial Erythrina alkaloids were isolated from the Erythrina variegata, E. crista-galli and E. arborescens (Fabaceae). The structures of these alkaloids were determined by spectroscopic analyses. Their possible formations were proposed. All isolated compounds showed no cytotoxicity and hypoglycemic activity at cell screening bioassay.

Isoquinoline alkaloids reduce beta-amyloid peptide toxicity in Caenorhabditis elegans

Alzheimer’s disease (AD) is a multifactorial health problem widespread over the world. Regarding the historical importance of the alkaloids in the central nervous system pharmacology they remain as promising drug candidates against AD. Seven alkaloids from Amaryllidaceae and Fabaceae were evaluated in vivo, in vitro and in silico targets related to the AD pathophysiology. Erythraline and erysodine showed the greatest potential compared to Memantine, a drug currently used in AD therapy, by delaying the Aβ1-42-induced paralysis in the transgenic strain CL2006 Caenorhabditis elegans, an alternative model to assess the impairment of beta-amyloid peptide deposition. The in vitro inhibition of the acetylcholinesterase was observed for the first time for Erythrina alkaloids; however Lycorine was the most active. Docking simulation contributed to comprehend this potential by showing a hydrophobic interaction between acetylcholinesterase and Lycorine in the amino acid residue TRP 84 as well as hydrogen bonds with TRY 121 and ASP 72.

Development of a Divergent Route to Erythrina Alkaloids

Erythrina alkaloids were identified at the end of the 19th century and today, more than 100 members of the erythrinane family have been isolated. They are characterized by a unique tetracyclic, α-tertiary spiroamine scaffold. Herein we detail our efforts towards the development of a divergent enantioselective synthesis of (+)-dihydro-β-erythroidine (DHβE) – one of the most prominent members of this intriguing family of natural products.1 Introduction2 Synthetic Strategy2.1 First Generation2.2 Second Generation2.3 Third Generation2.3.1 Radical Endgame2.3.2 Completion of the Total Synthesis3 Conclusion

Alkaloids from the stem barks of Erythrina stricta

Four previously undescribed erythrinan alkaloids, 8α-acetonylerythristemine, 8α-acetonylerysotrine, 10β-hydroxy-11β-methoxyerysotramidine and 3-epierysotrine, one undescribed pyrrolidine derivative, S-1-(4-hydroxy-3-methoxyphenethyl)-5-hydroxy pyrrolidin-2-one, and one undescribed amide, N-(3-hydroxy-4-methoxyphenethyl)-4-hydroxylbutanamide, along with thirteen known alkaloids were isolated from the stem barks of Erythrina strica Roxb. (Leguminosae). Their structures were identified by extensive analysis of physical, spectroscopic and spectrometric data. It's very interesting that the coexistence of 3-methoxytyramine, erythrinarbine, S-1-(4-hydroxy-3-methoxyphenethyl)-5-hydroxy pyrrolidin-2-one and N-(3-hydroxy-4-methoxyphenethyl)-4-hydroxylbutanamide that may be closely related in biosynthesis, supports the hypothetical biogenetic pathway of pyrrolo [2,1-a]isoquinoline alkaloids.

Erythrina alkaloids from leaves of Erythrina arborescens

Continued interest in Erythrina alkaloids resulted in the isolation of 38 alkaloids including 7 undescribed ones from the leaves of Erythrina arborescens Roxburgh. Among the new compounds, erythrivarines H-I were two dimeric alkaloids, while others were Erythrina alkaloid glucosides. Dimeric Erythrina alkaloids and monomers, turcomanidine and isoboldine, showed medium xanthine oxidase inhibition.

Enantioselective Total Synthesis of (+)-Dihydro-β-erythroidine.

Erythrina alkaloids represent a rich source of complex polycyclic, bioactive natural products. In addition to their sedative and hypotensive effect, their curare-like activity and structural framework have made them attractive targets for synthetic and medicinal chemists. (+)-Dihydro-β-erythroidine (DHβE), the most potent nicotine acetylcholine receptor antagonist (nAChR) of the Erythrina family, is synthesized for the first time in 13 steps from commercially available material.

EVALUATION OF MEMORY-ENHANCING ACTIVITY FOR ERYTHRININE FROM LEAF EXTRACT OF ERYTHRINA INDICA

Objective: The objective of the study was to investigate the memory-enhancing activity for erythrinine (ring-c-oxygenated Erythrina alkaloid) from leaf extract of Erythrina indica in mice.
 Methods: The study protocol designed in the way that it was carried out for 21 successive days by administrating the 5 mg/kg, s.c doses of isolated erythrinine to mice and the profile was challenged against the mice feeds with normal saline as a positive control and the mice treated with 5 mg/kg, s.c corticosterone as a negative control for the amnesia using Morris water maze test method.
 Results: Erythrinine-administered mice are showing remarkable retention of the memory (9.07±0.52) on the 21st day as such of the positive control normal saline (10.14±0.22) and against the negative control corticosterone-injected mice (70.86±0.54).
 Conclusions: The dose of 5 mg/kg s.c of isolated erythrinine from the leaf of E. indica shows the remarkable memory enhancement when it was investigated with the memory weakening induced test by corticosterone in mice’s using 5 mg/kg s.c. However, further studies required to elucidate the exact mechanism of action for developing its as potent memory-enhancing drug.

Isolation of erythrinan alkaloids from the leaves and flowers of Erythrina speciosa

In this paper, we describe the extraction of three alkaloids from the leaves and flowers of Erythrina speciosa, a plant documented in the literature to possess a range of potential medicinal applications. Two alkaloids were isolated from both leaves and flowers, with erythrartine being isolated from both plant parts. In agreement with the literature, we also isolated erysotrine from the flowers. The second alkaloid isolated from the leaves, and reported in this species for the first time, was (+)-11β-hydroxyerysotramidine.

Development of an Efficient Synthesis of rac‐3‐Demethoxyerythratidinone via a Titanium(III) Catalyzed Imine‐Nitrile Coupling

We herein describe the evolution of a rapid, high‐yielding synthesis of the erythrina alkaloid 3‐demethoxyerythratidinone. The natural product is assembled in six steps from commercial precursors in 30–35 % overall yield and with only two chromatographical purification operations. The key step is a titanium(III) catalyzed umpolung reaction in form of a reductive imine–nitrile coupling that can be combined with a subsequent cyclization reaction on a 50 mmol scale. Furthermore, optimized Wacker oxidation conditions enable the selective alkene oxidation in the presence of a tertiary amine functionality, which has been a problem in previous syntheses of erythrina alkaloids. The racemic route can be used to prepare the natural product on gram scale and the results may be useful for the synthesis of related alkaloids.

Antimicrobial Evaluation of Erythrinan Alkaloids from Erythrina cristagalli L.

Several species of the genus Erythrina have been used as sedative, antidepressant, and anticonvulsant. Erythrina crista-galli is native to the Pampa Biome and is widely used for medicinal purposes. Erythrinan alkaloids exhibit a range of pharmacological properties. The aim of this study was to evaluate the basic fractions and the alkaloids isolated from E. crista-galli bark against a collection of bacteria and fungi for the first time. Erythrina crista-galli stem bark was extracted with MeOH under reflux. The crude extract was dissolved in water, acidified and extracted with diethyl ether. Basification of the aqueous solution followed by diethyl ether and ethyl acetate extractions gave the basic ether and basic ethyl acetate fractions. Chromatographic purification of these fractions afforded five known alkaloids: erytharbine (1), erysotrine (2), erysotramidine (3), erysotrine N-oxide (4) and erythratidine (5) along with a new alkaloid named here erythratidine N-oxide (6). Alkaloids 1-6 were investigated against a collection of bacteria and fungi using the broth micro dilution method. In this work, a new alkaloid was isolated from E. crista-galli. The most significant bacterial inhibitory effect of alkaloidal fractions was observed against the Gram-negative Pseudomas aeroginosa (MIC values of 31.25 µg.mL-1). Basic ether fraction displayed good antimicrobial activity against Shigella sonnei with MIC= 62.5 µg.mL-1. Isolated alkaloids 1-6 showed inhibitory activity against all bacteria tested (MIC values of 50-100 µg.mL-1). In addition, the crude extract and alkaloids 1, 2, and 5 also showed good antifungal potential against Candida krusei (MICs between 12.5 and 31.25 µg.mL-1). The previously undescribed alkaloid 6 presented MIC values between 50 and 100 µg.mL-1 against all tested microorganisms. In general, as with a considerable number of phytochemicals with antimicrobial activity, alkaloids 1-6 may be considered with potential as antibacterial/antifungal agents. The MIC values of the extract, alkaloidal fractions and compounds 1-6 indicate that, at least in part, the isolates were responsible for the antimicrobial activity observed.

Alkaloids from flowers of Erythrina corallodendron

Two new Erythrina alkaloids, 10-oxo-erythrinine (1) erythrinine N-oxide (2) together with 23 known ones were obtained from the flowers of Erythrina corallodendron. The structures were determined based on analysis of their spectroscopic data. All compounds were first isolated from plants of Erythrina corallodendron.

An Update of Erythrinan Alkaloids and Their Pharmacological Activities.

The period of the past 5 years has witnessed a remarkable increase in all of the number, structural variety, and complexity of erythrinan alkaloids reported. This structural diversity seems to be most pronounced in the alkaloids reported from the two species Erythrina arborescens and Erythrina variegata. Between them, work-up of these taxa yielded new polymeric (dimeric and trimeric) erythrinan alkaloids, a first example in one case where a normal 6,5,6,6-membered indoloisoquinoline spirocylic core has rearranged to a spiro-fused 6,5,7,6-skeleton. Furthermore, erythrinan alkaloids with a fifth ring containing a 2H-imidazole functionality were also reported for the first time, together with some new structures having an unusual substitution and with functionalities at positions C-3 and C-7 of the erythrinan core. This contribution has included 40 more erythrinan alkaloids that are either new or were omitted in the most recent major reviews on the same topic, leading to a total of 154 known erythrinan alkaloids to date. There are a few cases where the structures of the new alkaloids are contestable due to insufficient data having been obtained on isolation. To facilitate easier reference and identification, all structures having a common core have been placed in the same table or figure in this chapter.The reported pharmacological activities of the new and known erythrinan alkaloids documented have shown a considerable bias towards central nervous system and related activities. Other prominent activities that have been reported are antifeedant, insecticidal, cytotoxic, antiprotozoal, anti-inflammatory, antioxidant, antifungal, and antiviral effects. Erythrinan alkaloids generally seem to lack antibacterial activity. Several new polymeric alkaloids were found to lack cytotoxicity against a number of human cancer cell lines, although two of them showed moderate aphicidal activity and one exhibited weak to moderate acetylcholinesterase inhibition. The biological activity of erythrinan alkaloids seems to be influenced by basic substructural requirements, such as a conjugated diene (Δ1,2, Δ6,7) system and is modulated by the presence (or absence) of other groups in rings A, B, C, and D of the erythrinan core. The erythrinan core may provide potential leads to structures that eventually may be useful therapeutically.In recent years, a number of stereoselective chemical synthesis methods have been applied towards the erythinan alkaloids, and these are described in this contribution.

Synthetic Studies on Heteropolycyclic Natural Products: Development of Divergent Strategy.

The divergent total syntheses of three types of heteropolycyclic natural products, namely gelsedine-type alkaloids, amathaspiramide alkaloids, and erythrina alkaloids, are outlined. A strategy involving a late-stage pluripotent common synthetic intermediate prepared via original and innovative transformations was employed. A brief description of the philosophy and criteria for choosing the synthetic targets and common synthetic precursors, as well as details regarding the development of the overall synthetic schemes from a common intermediate are discussed.

Chemical analysis of the Alphaproteobacterium strain MOLA1416 associated with the marine lichen Lichina pygmaea

Alphaproteobacterium strain MOLA1416, related to Mycoplana ramosa DSM 7292 and Chelativorans intermedius CC-MHSW-5 (93.6% 16S rRNA sequence identity) was isolated from the marine lichen, Lichina pygmaea and its chemical composition was characterized by a metabolomic network analysis using LC-MS/MS data. Twenty-five putative different compounds were revealed using a dereplication workflow based on MS/MS signatures available through GNPS (https://gnps.ucsd.edu/). In total, ten chemical families were highlighted including isocoumarins, macrolactones, erythrinan alkaloids, prodiginines, isoflavones, cyclohexane-diones, sterols, diketopiperazines, amino-acids and most likely glucocorticoids. Among those compounds, two known metabolites (13 and 26) were isolated and structurally identified and metabolite 26 showed a high cytotoxic activity against B16 melanoma cell lines with an IC50 0.6 ± 0.07 μg/mL.

Bioassay-guided isolation of potent aphicidal Erythrina alkaloids against Aphis gossypii from the seed of Erythrina crista-galli L.

The cotton aphid (Aphis gossypii Glover) is one of the most invasive pests of cotton. Many botanical phytochemicals have a long history as a source of insecticides, and as templates for new insecticides. This study was undertaken to isolate aphicidal compounds from the seeds of Erythrina crista-galli L. using the bioassay-guided isolation method. Three novel and 11 known Erythrina alkaloids were isolated. Erysodine (9), erysovine (10), erysotrine (8) and erythraline (11) showed moderate to excellent aphicidal activity with LD50 values of 7.48, 6.68, 5.13 and 4.67 ng aphid-1 , respectively. The Potter spray tower bioassay gave corresponding LC50 values of 186.81, 165.35, 163.74 and 112.78 µg ml-1 . A unique substructure, which presents an sp3 methylene at C-8, a non-oxygenated site at N-9 and a conjugated dienes group (Δ1,2 and Δ6,7 ), plays a crucial role in the aphicidal activity. Application of erythraline (11) led to different increases in the activities of superoxide dismutase, catalase and glutathione S-transferase. The study demonstrated that the Erythrina alkaloids erysodine (9), erysovine (10), erysotrine (8) and erythraline (11) have potential use as botanical aphicides for commercial application, or as templates for the development of new insecticides. © 2017 Society of Chemical Industry.

A New Erythrinan Alkaloid Glycoside from the Seeds of Erythrina crista-galli.

A new Erythrina alkaloid glycoside, named erythraline-11β-O-glucopyranoside, was isolated from the seeds of Erythrina crista-galli L., together with five known Erythrina alkaloids and an indole alkaloid. The structure of the new alkaloid glycoside was elucidated by spectroscopic methods, and all of the compounds were evaluated for their antiviral activity against tobacco mosaic virus.

3D‐Printed Polypropylene Continuous‐Flow Column Reactors: Exploration of Reactor Utility in SNAr Reactions and the Synthesis of Bicyclic and Tetracyclic Heterocycles

3D printing has the potential to transform the way in which chemical reactions are carried out due to its low‐cost, ease‐of‐use as a technology and its capacity to expedite the development of iteratively enhanced prototypes. In this present study, we developed a novel, low‐cost polypropylene (PP) column reactor that was incorporated into an existing continuous‐flow reactor for the synthesis of heterocycles. The utility and solvent resistance of the printed devices were explored in SNAr reactions to produce substituted aniline derivatives and in the synthesis of bicyclic and tetracyclic heterocycles. Using this approach, a range of heterocyclic compounds was synthesised including the core structure of the natural product (±)‐γ‐lycorane and structurally complex compounds based on the tetracyclic core of the erythrina alkaloids.

Synthesis of a tetracyclic core of Erythrina alkaloids and analogs of crispine A

Both enantiomers of C10b methyl analogs of crispine A and a tetracyclic core of Erythrina alkaloids were synthesized starting from l-aspartic acid via a common chiral N-arylethyl succinimide intermediate. The pivotal C10a-C10b bond formation and construction of the C10b stereogenic center were achieved via diastereoselective N-acyliminium ion cyclization. The dibenzylamino group gave stereochemical control where 1,2- and 1,3-stereoinductions led to the cyclized products with opposite configurations at the newly generated stereogenic center. Cope elimination of the dibenzylamino group gave a cyclic enamide which underwent Michael addition and ring closing metathesis of the resulting bis-allyl intermediate in the synthesis of a tetracyclic core of Erythrina alkaloids.

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE.

We report an effective synthetic protocol to access [6,6]-bicyclic lactone moieties through a regio- and stereoselective intramolecular Mizoroki–Heck cross-coupling reaction followed by a 6π-electrocyclization. This method enabled the first synthesis of the elusive CD fragment of the Erythrina alkaloid DHβE. Preliminary pharmacological evaluations support the notion that the key pharmacophores of DHβE are located in the A and B rings.