HPLC-DAD-SPE-NMR isolation of tetracyclic spiro-alkaloids with antiplasmodial activity from the seeds of Erythrina latissima

Abstract

Seven tetracyclic spiro-alkaloids, i.e. glucoerysodine (1), erysodine (2), epi-erythratidine (3), erysovine (4), erythratidine (5), erysotrine (6) and erythraline (7) were isolated from the seeds of Erythrina latissima by means of conventional separation methods and HPLC-DAD-SPE-NMR. Their structures were elucidated by spectroscopic means. This is the first report on the isolation of compounds 3, 5 and 6 from this plant. Antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and cytotoxicity against MRC-5 cells (human fetal lung fibroblast cells) was assessed in vitro. Erysodine (2) and erysovine (4) showed moderate activity (IC₅₀ 6.53?µM and 4.05?µM, respectively), compared with the standard chloroquine (IC₅₀ = 0.14?µM). No cytotoxicity was observed in a concentration up to 64.0?µM.     

Excelsanone,a new isoflavonoid from Erythrina excelsa (Fabaceae), with in vitro antioxidant and in vitro cytotoxic effects on prostate cancer cells lines

Abstract

A new isoflavonoid, excelsanone (2), was isolated from the ethyl acetate extract of Erythrina excelsa stem bark, together with three known compounds namely 6,8-diprenylgenistein (3), β-sitosterol (1) and sitosteryl-β-D-glucopyranoside (4). Their structures were elucidated using spectroscopic methods (HR-ESI-MS, NMR and IR) and by comparison with some literature data. The antioxidant activity of crude extracts and two isolated compounds was evaluated using free radical scavenging (DPPH) and Ferric Reducing Ability Power (FRAP) methods with catechin as standard. The results of the radical scavenging activity showed that excelsanone (2) has a moderate potential with an IC₅₀ of 1.31?mg/ml. The cytotoxicity of compounds 2 and 3 as well as the ethyl acetate extract was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in two prostate cancer cell lines (DU145 and PC3). Excelsanone (2) induced a greater cytotoxicity in all tested cell lines, with a significant inhibition of DU145 cells growth in a concentration-dependent manner.     

Synthetic Studies on Erythrina Alkaloids: Formal Total Synthesis of (+)-3-Demethoxyerythratidinone

A formal asymmetric synthesis of (+)-3-demethoxyerythratidinone (1) is reported using the key intermediate 3 as the starting material, which is available from L-malic acid by a known method.

A new erythrinan N-oxide alkaloid from Erythrina stricta

This phytochemical study of stems and leaves of Erythrina stricta led to the isolation of twenty-three alkaloids, one of them previously unreported, 11β-hydroxyerythratidine N-oxide. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic analyses including HSQC, HMBC, ¹H–¹H COSY, NOESY, as well as HRESIMS data in addition to comparison with reports in the literature.     

Three Prenylated Isoflavones from Erythrina variegate

Two new prenylated isoflavones (erythrivarones A and B) were isolated from the stem bark of Erythrina variegata Linn, together with the known compound alpinumisoflavone (1). The structures of erythrivarones A and B were characterized as dihydroalpinumisoflavone (2) and 4′-hydroxy-[6″,6″-dimethyldihydropyrano(2″,3″:5,6)]-[6?,6?-dimethyldihydropyrano(2?,3?:7,8)]isoflavone (3), respectively, by means of spectroscopic analysis.     

Unprecedented new nonadecyl para-hydroperoxycinnamate isolated from Erythrina excelsa and its cytotoxic activity

A new unprecedented cinnamate derivative (1) was obtained from Erythrina excelsa (Leguminosae) and identified as nonadecyl para-hydroperoxycinnamate. This compound was isolated together with three known compounds, namely lupeol (2), mixture of sitosterol and stigmasterol (3), and isoneorautenol (4). Their structures were established on the basis of NMR and mass spectroscopic data in conjunction with those reported in the literature. Compound 1 was evaluated for its capability of inhibiting cancer cell lines and growth of a panel of microbial strains. It turned out that 1 is moderately to significantly cytotoxic against six cancer cell lines and shows weak to no antimicrobial activity.     

Erythrinarbine,a Novel nor-A ring Erythrina Alkaloid from Erythrina arborescens

ErythrinaarborescensRoxb.belongstoErythrinagenusofPapilionaceaefamilyplants,andiswidelydistributedintropicalandsubtropicalregionsoftheworld,aswellasinthesouthandsouth-westofChina'.AsaChinesefolkmedicine,itsrootandstemareusedtotreatrheumatismanddysentery'.TheErythrinaalkaloids,normallyaC.,tetracyclicspiroaminesystem,erythrinanel,arethecharacteristicconstituentsinErylhrinagenusandabout100erythrinaalkaloidshavebeensofarreportedfromthisgenusplants'-'.MostoftheseErythrinaalkaloidshaveatetrahydr…     

Mixture designs for exploring class diversity and metabolite fingerprinting: an efficient column chromatographic strategy

The effects of four solvents, hexane, dichloromethane, ethyl acetate, methanol, and their mixtures on the separation of metabolites in crude extracts of Erythrina speciosa Andrews leaves were investigated using two strategies for open column chromatography. The classical extraction procedure was compared with mobile phases prepared according to a mixture design in order to explore the effects of solvent interactions on metabolite separations. Principal component analysis was used to compare the UV spectra obtained from RP-HPLC-DAD and to estimate the number of independent factors contained in the chromatographic data of the extracts. The results showed that, in addition to solvent polarity, solvent mixtures play an important role in metabolite separation. When pure solvents are used, larger groups of similar spectra are observed in the factor analysis score graphs indicating the same or a limited number of metabolite classes. In contrast solvent mixtures produced score graphs with a larger number of clusters indicating greater metabolic diversity. Besides resulting in more peaks than the pure solvents the chromatographic data of the design mixtures resulted in larger numbers of significant principal components confirming the greater chemical diversity of their extracts. Thus, if the objective of an analysis is to obtain metabolites of the same class, one should use pure solvents. On the other hand, binary and ternary solvent mixtures are recommended for more efficient investigations of class diversity and richer metabolite fingerprints.     

Fukiinsäure und 3′-O-Methyl-fukiinsäure,zwei phenolische Hydroxycarbonsäuren aus Piscidia Erythrina

Purification of crude piscidic acid from ‘Cortex Piscidiae Erythrinae’, the root bark of Piscidia Erythrina L. (Papilionaceae), led to the isolation of fukiic acid (5) and 3′-O-methyl-fukiic acid (8). Since partition chromatography with alcoholic solvents produced the corresponding half-esters as artefacts, the acids were transformed to their methyl esters before separation. Spectroscopic methods and comparison with authentic samples from Petasites japonicus F. SCHMIDT (Compositae) confirmed the structures 5 and 8 .     

Statistical mixture design investigation of fractionated and total extracts from Erythrina speciosa Andrews leaves

The simplex centroid mixture design for the ethanol, dichloromethane, hexane and acetone solvents has been applied to the extraction of crude mass and the fiber, organic, neutral and basic fractions as well as the fractionation residues of Erythrina speciosa Andrews leaves. Binary and ternary synergic solvent interactions are seen to provide dominant contributions to the extraction of both crude mass and all the fractions. Quadratic and special cubic mixture models precisely predict the extracted quantities of each fraction and the residue as a function of the proportions of the four solvents. Different solvent mixtures are found to be the most efficient extractors for the different fractions: binary dichloromethane‐hexane mixtures for the fiber fraction, ternary ethanol‐dichloromethane‐acetone mixtures for the neutral fraction, binary ethanol‐dichloromethane mixtures for the organic fraction, crude extract and residue values and ternary ethanol‐dichloromethane‐hexane mixtures for the basic fraction. Principal component analysis shows that the ethanol‐dichloromethane mixtures are important for extracting large quantities of the basic and organic fractions as well as of the residue and crude masses.     

Synthesis of canthine/erythrinane alkaloid analogs

The pentacyclic lactams9,11, and14 were prepared using a thermal condensation of tryptamine with symmetrical oxodiesters3 and4 as the key step. The formation of the ring E in the tetracyclic compounds5,6,8,10,12, and13 is strongly dependent on the ring size.

---

Synthese von Analoga der Canthin/Erythrina Alkaloide (Kurze Mitteilung)

Zusammenfassung Die pentacyclischen Verbindungen9,11 und14 wurden durch thermische Kondensation von Tryptamin mit symmetrischen Oxodiestern3 und4 als wichtigster Reaktionsstufe dargestellt. Die Bildung des Ringes E in den tetracyclischen Verbindungen5,6,8,10,12 und13 ist stark von der Ringgröße abhängig.

     

Principal component and Tucker3 analyses of high performance liquid chromatography with diode-array detection fingerprints of crude extracts of Erythrina speciosa Andrews leaves

Mixtures of ethanol, dichloromethane, hexane and acetone obtained according to a statistical design have been used to extract substances from Erythrina speciosa Andrew leaves for chromatographic fingerprinting. The plant extracts from each mixture were analyzed by HPLC-DAD providing UV–vis spectra for each chromatographic peak. These chromatograms and spectra for the design mixtures were then treated with principal component (PCA), Tucker3 and PARAFAC analyses. PCA indicated the existence of five different chromatographic fingerprints for the leave extracts depending on the solvent mixture composition. Different chromatographic peak areas were strongly correlated with the mixture proportions of acetone, dichloromethane and ethanol. Tucker3 and PARAFAC analyses were very useful for identifying simultaneous correlations between chromatographic peak areas, spectral band absorbances and solvent proportions. The acetone proportion was highly correlated with the area of the 3.69 min retention time peak and the spectral absorbances between 250 and 260 nm, consistent with the presence of natural polyphenols. The dichloromethane mixture proportion was strongly correlated with the 12.19 min chromatographic peak area and a single spectral absorbance at 201 nm. This spectral absorption is characteristic of the electronic structures of terpenes and alkaloids.     

An overview of techniques and strategies for isolation of flavonoids from the genus Erythrina

Plants in the genus Erythrina is a potential source of chemical constituents, one of which is flavonoids, which have diverse bioactivities. To date, literature on the flavonoids from the genus Erythrina has only highlighted the phytochemical aspects, so this review article will discuss isolation techniques and strategies for the first time. More than 420 flavonoids have been reported in the Erythrina genus, which are grouped into 17 categories. These flavonoid compounds were obtained through isolation techniques and strategies using polar, semi-polar, and non-polar solvents. Various chromatographic techniques have been developed to isolate flavonoids using column flash chromatography, quick column chromatography, centrifugally accelerated thin-layer chromatography, radial chromatography, medium-pressure column chromatography, semi-preparative high-performance liquid chromatography, and preparative high-performance liquid chromatography. Chromatographic processes for isolating flavonoids can be optimized using multivariate statistical applications such as response surface methodology with central composite design, Box–Behnken design, Doehlert design, and mixture design.     

A new sesquiterpenoid from Polyalthia petelotii

A new sesquiterpenoid (?)-ethyl dihydrophaseate (1) was isolated from the stems and leaves of Polyalthia petelotii, together with two clerodane diterpenoids, 16α-hydroxycleroda-3,13(14)Z-dien-15,16-olide (2), 15-hydroxy-cis-ent-cleroda-3,13(E)-diene (3), a eudesmane sesquiterpenoid, eudesm-4(15)-ene-7α,11-diol (4), an aromatic aldehyde, vanillin (5), a bisisoquinolines alkaloid, spinosine (6) and an aporphine alkaloid, (?)-oliveroline-β-N-oxide (7). Their structures were established by extensive spectroscopic analysis, including 2D-NMR techniques. Compounds 3, 4 and 6 were isolated from the genus Polyalthia for the first time and the others obtained originally from P. petelotii. The isolates were assessed for their cytotoxicity against five human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result showed that only 2 displayed weak inhibitory activity.     

A new ent-kaurane diterpenoid from Ixora amplexicaulis

A new ent-kaurane diterpenoid, 6α,16α-dihyroxy-ent-kaurane (1), was isolated from the stems of Ixora amplexicaulis, together with (24R)-6β-hydroxy-24-ethyl-cholest-4-en-3-one (2), 7β-hydroxysitosterol (3), maslinic acid (4), 3,3′-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran) (5) and protocatechuric acid (6). Their structures were established by extensive spectroscopic analysis, including 2D NMR techniques. Compounds 2–5 were isolated from the genus Ixora for the first time and 6 obtained originally from I. amplexicaulis.     

The Novel N,S-Substituted Halonitrodienes from the Reactions of Thiosubstituted Nitrodiene with Piperazine and Morpholine

The substituted 1,2-dibromomethanethio nitrodiene 2 was obtained from the addition of bromine to S-substituted nitrodien 1 in carbon tetrachloride. N, S-substituted compounds 4a–h were synthesized from the reactions of compound 2 with several substituted piperazine derivatives 3a–h in dichloromethane. N, S-substituted compounds 6 and 8 were synthesized from the reaction of 2 with morpholine ( 5 ) and thiomorpholine ( 7 ) in dichloromethane, respectively. Dibutadienyl piperazines 10 , 12 , and 14 were synthesized from the reactions of 2 with homopiperazine ( 9 ), piperazine ( 11 ), and 2,5-dimethylpiperazine ( 13 ), respectively.     

A new Secondary metabolites of the crinoid (Comanthina schlegeli) associated fungus Alternaria brassicae 93

Fungus Alternaria brassicae 93 isolated from crinoid (Comanthina schlegeli), which was collected from the South China Sea. Six compounds were isolated from A. brassicae 93, including one new compound (1), along with five known compounds, ochratoxin A methyl ester (2), cis-4-hydroxym-ellein (3), (R)-7-hydroxymellein (4), trans-2-anhydromevalonic (5) and protocatechuic acid (6). Their structures were determined by spectroscopic methods and comparison with reported data. Cytotoxicity against two human cancer cell lines and antibacterial activity against twelve aquatic bacteria of compound 1 were also tested.     

Lanostane triterpenoids from cultivated fruiting bodies of the basidiomycete Ganoderma australe

A new lanostane triterpene (1), together with three known compounds (2–4), were isolated from cultivated fruiting bodies of the basidiomycete Ganoderma australe. The structure was elucidated on the basis of NMR spectroscopic and mass spectrometry data. The olefinic geometry of methyl australate (2) was revised from 20(22)Z to 20(22)E. These compounds (1–4) were different from the lanostanes isolated from mycelial cultures of the same strain source.     

A new sesquiterpene from Kalimeris integrifolia

A new sesquiterpene kalinturoside A (1), and 17 known compounds friedelan-3-ol (2), 24-ethyl-5a-cholesta-7, 22(E)-dien-3-one (3), friedelin (4), syringaresinol (5), α-spinasterol (6), ciwujiatone (7), syringic acid (8), scopoletin (9), apocynin (10), 1-(3-hydroxy-4, 5-dimethoxyphenyl)ethan-1-one (11), apigenin (12), 5-hydroxymethylfurfural (13), stigmasterol-3-O-β-d-glucopy-ranoside (14), bidenoside C (15), citrusin (16), irioresinol A (17) and syringaresinol-4-O-β-d-glucopyranoside (18) were isolated from the herbs of Kalimeris integrifolia. The structures of these compounds were elucidated using spectroscopic techniques such as NMR and MS. All of the compounds were isolated from this genus for the first time.