Alkaloid Glucosides Research Articles

Glycoalkaloids: Structural diversity and pharmacological activities

Glycoalkaloids (GAs) are a class of special secondary metabolites found in plants. Studies have found that they have a wide range of pharmacological activities, such as antiviral, antifungal, and anticancer properties, with significant potential for development and utilization value. At present, alkaloid glucosides mainly fall into 2 categories: indole alkaloid glucosides and steroid alkaloid glucosides. In addition, there are small amounts of quinolines, isoquinolines, isoguanines, and other alkaloids. At present, only a few of the GAs have been found, which is inconsistent with the diversity of alkaloids. In addition, only a few GAs have been isolated and identified. This paper reviews the natural alkaloid glycosides from the perspectives of structural classification and pharmacological activity. It analyzes the reasons for the limited number of isolated components and proposes a rational separation method based on the literature. To provide references for the separation, identification, and bioactivity of glycoalkaloids.

Copper-Catalyzed C2- or C3-Thioglycosylation of Indoles with N-(Thioglycosides)succinimides: An Effective Strategy for the Total Synthesis of Isatindigotindolosides.

Isatindigotindolosides, indoles containing a 1-S-β-glucopyranosyl unit at position C2, show promising bioactivity. Here, we report a copper-catalyzed C2- or C3-thioglycosylation of indoles with N-(thioglycosides)succinimides to construct indole alkaloid glucosides. This reaction is widely tolerant of functional groups, as various indoles and thioglycosides are suitable. It also provides a reliable method for performing late-stage modifications of natural products, such as gramine and melatonin. Total syntheses of isatindigotindolosides I and II were successfully accomplished using the C2-thioglycosylation reaction as a key step.

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.

A new indole alkaloid, antioxidant and antibacterial activities of crude extracts from Saccocalyx satureioides

The new acylated indole alkaloid glucoside indole-3-carboxylic acid-(6'-O-caffeoyl)-β-D-glucoside 1 has been isolated from the ethyl acetate (EtOAC) extract of Saccocalyx satureioides Coss. & Dur. (Lamiaceae) together with eight known secondary metabolites 2-9. Two indoles 2 and 3, five methylated flavone aglycones 4-8 and one monoterpene glucoside 9 were reported for the first time in the genus Saccocalyx. The structural elucidation of these compounds was accomplished by spectroscopic methods including 1 D (1H and 13C) and 2 D (COSY, HSQC and HMBC) NMR techniques, and mass spectrometry, and by comparison with literature data. Light petroleum, EtOAc, chloroform and n-butanol (n-BuOH) extracts of S. Satureioides were screened for their antioxidant activity using DPPH radical scavenging and β-carotene bleaching methods. The antibacterial activity of these extracts indicates that n-BuOH and EtOAc extracts possess the strongest activity.

Indole alkaloid glucosides from the roots of Isatis indigotica

Five new indole alkaloid glucosides named isatindigotindolosides A-E (1–5), along with three known analogs (6–8), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including the absolute configurations were determined based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations. In the preliminary assays, compounds 1, 6 and 7 showed antiviral activity against influenza virus A/Hanfang/359/95 (H3N2) with IC50 values of 14.6–33.3 μM. Compound 1 also exhibited inhibitory effect against nitric oxide (NO) production in microglial cell BV2 with an inhibition ratio of 93.0% at 10 μM.

Indole alkaloid glycosides from the aerial parts of Strobilanthes cusia.

Three indole alkaloid glycosides, strobilanthosides A-C (1-3), two known indole alkaloid glucosides (4 and 5), and five phenylethanoid glycosides (8-10) were isolated from the aerial parts of Strobilanthes cusia. The structures of the new compounds were elucidated by spectrometric analysis, and the absolute configurations of 1 and 2 were established by ECD spectrocsopy. N'-β-d-Glucopyranosylindirubin (5) showed weak antibacterial activity (MIC 62.5-125 μM) against Staphylococcus aureus.

Ligand structures of synthetic deoxa-pyranosylamines with raucaffricine and strictosidine glucosidases provide structural insights into their binding and inhibitory behaviours

Insight into the structure and inhibition mechanism of O-β-d-glucosidases by deoxa-pyranosylamine type inhibitors is provided by X-ray analysis of complexes between raucaffricine and strictosidine glucosidases and N-(cyclohexylmethyl)-, N-(cyclohexyl)- and N-(bromobenzyl)-β-d-gluco-1,5-deoxa-pyranosylamine. All inhibitors anchored exclusively in the catalytic active site by competition with appropriate enzyme substrates. Thus facilitated prospective elucidation of the binding networks with residues located at <3.9 Å distance will enable the development of potent inhibitors suitable for the production of valuable alkaloid glucosides, raucaffricine and strictosidine, by means of synthesis in Rauvolfia serpentina cell suspension cultures.

Bis(monoterpenoid) indole alkaloid glucosides from Uncaria hirsuta

One novel bis(monoterpenoid) indole alkaloid glucoside, hirsutaside D ( 1), along with three known compounds, bahienoside A ( 2), bahienoside B ( 3) and neonaucleoside B ( 4), were isolated from the leaves of U. hirsuta. The structure of compound 1 was elucidated on the basis of extensive spectroscopic data analysis and chemical means. Characterization of compounds 2– 4 was based on spectral analysis and comparison with the literature. Their cytotoxic effects on four human tumor cell lines were examined.

Locustoside A — A new purine alkaloid glucoside from seeds of Gleditsia japonica

A new purine alkaloid glucoside designated locustoside A has been isolated from the seeds of Gleditsia japonica, which has been used in oriental traditional medicine. The structure was determined as 7-β- d-glucopyranosyl-3-(3-methyl-2-butenyl)-isoguanine by interpretation of spectroscopic data and was confirmed by X-ray crystallographic analysis.

Organ-specific and environmental control of accumulation of psychollatine, a major indole alkaloid glucoside from Psychotria umbellata

Psychollatine is an unusual indole alkaloid produced by Psychotria umbellata Vell, an Atlantic Forest understorey tree. Leaves, young inflorescences and fruit pulp displayed high amounts of psychollatine (from 2.5 to 4.5% dry wt). Seeds accumulated lower quantities (0.2% dry wt), and roots, trace amounts (0.06% dry wt). Alkaloid accumulation was not seasonally affected and leaf content was not significantly enhanced by wounding, exposure to salicylic acid, hydrogen peroxide, or UV. The alkaloid content in leaves decreased upon cutting exposure to auxin. Under strong UV, the amount of chlorophylls did not decrease compared to control contents at 48 and 72 h. Post-harvest psychollatine content in leaves was stable in different temperatures, except at 65 °C. Psychollatine was an effective singlet oxygen, superoxide, and peroxide quencher. These antioxidant properties and the constitutively high amount of psychollatine indicate a role for the alkaloid in oxidative stress responses.

The New β-D-Glucosidase in Terpenoid-Isoquinoline Alkaloid Biosynthesis in Psychotria ipecacuanha

Ipecac alkaloids produced in the medicinal plant Psychotria ipecacuanha such as emetine and cephaeline possess a monoterpenoid-tetrahydroisoquinoline skeleton, which is formed by condensation of dopamine and secologanin. Deglucosylation of one of the condensed products N-deacetylisoipecoside (1 alpha(S)-epimer) is considered to be a part of the reactions for emetine biosynthesis, whereas its 1 beta(R)-epimer N-deacetylipecoside is converted to ipecoside in P. ipecacuanha. Here, we isolated a cDNA clone Ipeglu1 encoding Ipecac alkaloid beta-D-glucosidase from P. ipecacuanha. The deduced protein showed 54 and 48% identities to raucaffricine beta-glucosidase and strictosidine beta-glucosidase, respectively. Recombinant IpeGlu1 enzyme preferentially hydrolyzed glucosidic Ipecac alkaloids except for their lactams, but showed poor or no activity toward other substrates, including terpenoid-indole alkaloid glucosides. Liquid chromatography-tandem mass spectrometry analysis of deglucosylated products of N-deacetylisoipecoside revealed spontaneous transitions of the highly reactive aglycons, one of which was supposed to be the intermediate for emetine biosynthesis. IpeGlu1 activity was extremely poor toward 7-O-methyl and 6,7-O,O-dimethyl derivatives. However, 6-O-methyl derivatives were hydrolyzed as efficiently as non-methylated substrates, suggesting the possibility of 6-O-methylation prior to deglucosylation by IpeGlu1. In contrast to the strictosidine beta-glucosidase that stereospecifically hydrolyzes 3 alpha(S)-epimer in terpenoid-indole alkaloid biosynthesis, IpeGlu1 lacked stereospecificity for its substrates where 1 beta(R)-epimers were preferred to 1 alpha(S)-epimers, although ipecoside (1 beta(R)) is a major alkaloidal glucoside in P. ipecacuanha, suggesting the compartmentalization of IpeGlu1 from ipecoside. These facts have significant implications for distinct physiological roles of 1 alpha(S)- and 1 beta(R)-epimers and for the involvement of IpeGlu1 in the metabolic fate of both of them.

Alkaloids from the Leaves of Uncaria rhynchophylla and Their Inhibitory Activity on NO Production in Lipopolysaccharide-Activated Microglia

Two new isomeric alkaloids, 18,19-dehydrocorynoxinic acid B (1) and 18,19-dehydrocorynoxinic acid (2), were isolated from the CHCl3 extract of the leaves of Uncaria rhynchophylla, together with four known rhynchophylline-type alkaloids, corynoxeine (3), isocorynoxeine (4), rhynchophylline (5), and isorhynchophylline (6), and an indole alkaloid glucoside, vincoside lactam (7). The structures of compounds 1 and 2 were elucidated by spectroscopic methods including UV, IR, HREIMS, 1D and 2D NMR, and CD experiments. The activity assay showed that compounds 3-6, with a C-16 carboxylic ester group, and 7 exhibited inhibitory activity on lipopolysaccharide (LPS)-induced NO release in primary cultured rat cortical microglia (IC 50: 13.7-19.0 microM). However, only weak inhibitory activity was observed for compounds 1 and 2, with a C-16 carboxylic acid group (IC 50: >100 microM).

Antimalarial Constituents fromNauclea orientalis (L.) L.

Bioassay-guided fractionation of the antimalarial-active CHCl3 extract of the dried stem of Nauclea orientalis (L.) L. (Rubiaceae) has resulted in the isolation of two novel tetrahydro-beta-carboline monoterpene alkaloid glucosides, naucleaorine (= (16alpha,17beta)-3,14:15,20-tetradehydro-16-ethenyl-17-(beta-D-glucopyranosyloxy)-19alpha-methoxyoxayohimban-21-one; 1) and epimethoxynaucleaorine (2), as well as the known compounds, strictosidine lactam (= (15beta,16alpha,17beta)-19,20-didehydro-16-ethenyl-17-(beta-D-glucopyranosyloxy)oxayohimban-21-one; 3), 3,4,5-trimethoxyphenol (4), 3alpha-hydroxyurs-12-en-28-oic acid methyl ester (5), 3alpha,23-dihydroxyurs-12-en-28-oic acid (6), 3alpha,19alpha,23-trihydroxyurs-12-en-28-oic acid methyl ester (7), and oleanolic acid (8). Compounds 1, 2, 6, and 8 showed moderate in vitro activities against Plasmodium falciparum. Their structures and configurations were elucidated by spectroscopic methods including 1D- and 2D-NMR analyses.

Specific accumulation and revised structures of acridone alkaloid glucosides in the tips of transformed roots of Ruta graveolens

The root tips of Ruta graveolens (common rue) show strong autofluorescence of acridone alkaloids, which are characteristic secondary metabolites of this plant. To study the specific distribution and accumulation of acridone alkaloids in various root segments of Ruta graveolens, root material was harvested from genetically transformed root cultures and extracts were investigated by chromatographic techniques and HPLC- 1H NMR spectroscopy. The cells of the elongation and differentiation zones contained acridone glucosides and large amounts of acridone alkaloids, mainly rutacridone. Gravacridondiol glucoside was identified as the dominant secondary compound of the root tips and its structure revised by means of spectroscopic methods. In addition, minor acridones, including the structurally revised gravacridontriol glucoside and unknown natural products, were found in the root tip.

Novel bis(monoterpenoid) indole alkaloids from Psychotria bahiensis.

Two new bis(monoterpenoid) indole alkaloid glucosides, bahienoside A (1) and bahienoside B (2), together with five known compounds, 5alpha-carboxystrictosidine, angustine, strictosamide, and (E)- and (Z)-vallesiachotamine, were isolated from the aerial parts of Psychotria bahiensis collected in Trinidad, West Indies. The structures of the compounds were elucidated using 1D and 2D NMR spectral methods, viz., (1)H, (13)C, (13)C DEPT, (1)H-(1)H COSY, HSQC, HMQC, HMBC, and TOCSY aided by IR, UV, and circular dichroism measurements.

Alkaloide aus Veratrum patulum, I. Isolierung und Strukturaufklärung neuer Steroidalkaloidglycoside

Alkaloids from Veratrum patulum, I. – Isolation and Structure Elucidation of New Steroid Alkaloid GlycosidesHerrn Professor Dr. F. Zymalkowski zum 80. Geburtstag gewidmet. Beside the known veratrosine (1), two new steroid alkaloid glucosides, 23‐O‐β‐D‐glucopyranosyl‐20‐isoveratramine (2) and (22S,23R,25S)‐23‐O‐β‐D‐glucopyranosyl‐5,11,13‐veratratrienine‐3β,23‐diol (3), were isolated from the roots of Veratrum patulum Loes. fil. (Liliaceae) and characterized by spectroscopic methods.

Two steroidal alkaloid glycosides from Veratrum taliense

Two new verazine type alkaloid glucosides, veramiline-3- O-β- d-glucopyranoside and stenophylline B-3- O-β- d-glucopyranoside have been isolated from the hypogeal parts of plants of Veratrum taliense. Their structures were established by spectroscopic data and chemical evidence.

A New Indole Alkaloid Glycoside from the Leaves ofPalicourea marcgravii

A new indole alkaloid glucoside, named palicoside, has been isolated from the leaves of PALICOUREA MARCGRAVII (Rubiaceae) collected in Brazil. The structure was established by spectroscopic methods and its chemical conversion to strictosamide.

Hypotensive principles of Uncaria hooks.

A methanol extract of the Oriental crude drug “chōtōkō”, Uncaria hooks, elicited a strong and long-lasting hypotension on injection into rats. The activity differed considerably from the effects expected for the known constituents, rhynchophylline and its analogues, which elicit only weak transient hypotensive effects. Fractionation of the extract, along with the pharmacological assays, resulted in isolation of three indole alkaloid glucosides, cadambine (1), 3α-dihydrocadambine (2) and 3β-isodihydrocadambine (3). The former (1) was found inactive but the latter two (2 and 3) exhibited strong and long-lasting hypotensive actions similar to the extract. 3β-Dihydrocadambine (4), which was not detected in the extract, also showed a strong hypotensive activity.

Variability of Amino Acids, Protein, Vicine and Convicine in Vicia faba (L) Cultivars

ABSTRACTSamples of 10 varieties of broad bean were analyzed for dry matter, crude protein, amino acids and alkaloid glucosides. The varieties “Korunde” and “Supersimonia” showed the highest protein content; the amino acid composition was similar in all varieties. Sulfur‐amino acids were limiting in all tested varieties. The varieties “Gemini” and “Locale di Putignano” showed the highest content of total alkaloid glucosides. It was noticed that variety “Supersimonia”, able to produce 1870 kg/ha, shows also a high protein content and a low antinutritional factor content. The results of this work supply information to the breeder about varieties with low content of antinutritional factors.