Antiangiogenic phenylpropanoid glycosides from Gynura cusimbua

A new phenylpropanoid glycoside, named α-L-rhamnopyranosyl-(1?2)-β-D-[4″-(8E)-7-(3,4-dihydroxyphenyl)-8-propenoate, 1″-O-(7S)-7-(3,4-dihydroxyphenyl)-7-methoxy-ethyl]-glucopyranoside (1), together with nine known compounds (2–10) were isolated from the active fraction (n-Butanol fraction) of Gynura cusimbua for the first time. The known compounds (2–10) were identified as phenylpropanoid glycosides on the basis of extensive spectral data and references. The antiangiogenic activities of compounds (1–10) were evaluated by MTT assay on HUVECs and wild-type zebrafish in vivo model assay. As a result, compounds 1, 6, 7, 8 and 10 exhibited certain antiangiogenic activities.     

Structure determination and quantification of a new flavone glycoside with anti-acetylcholinesterase activity from the herbs of Elsholtzia ciliata

Three acacetin triglycosides (compounds 1, 2 and 3) were isolated from the herbs of Elsholtzia ciliata (Labiatae). The structure were identified as 7-O-β-D-glucopyranosyl-(1 → 2)[α-L-rhamnopyranosyl-(1 → 6)]-β-D-glucopyranoside (compound 1), 7-O-(6-O-acetyl)-β-D-glucopyranosyl-(1 → 2)[α-L-rhamnopyranosyl-(1 → 6)]-β-D-glucopyranoside (compound 2) and 7-O-(6-O-acetyl)-β-D-glucopyranosyl-(1 → 2)[(4-O-acetyl)-α-L-rhamnopyranosyl-(1 → 6)]-β-D-glucopyranoside (compound 3) of acacetin. The structures of these compounds were determined on the basis of 2D-NMR spectroscopic data. Compound 3 has not been isolated from a natural source. In addition, the three compounds were quantitatively analysed by HPLC. Acetylcholinesterase (AChE) inhibition activity was assayed to find anti-Alzheimer’s activity, since this enzyme increases the concentration of acetylcholine (ACh), a neurotransmitter, responsible for brain’s memory. Acacetin, the aglycone of the three compounds, exhibited a potent anti-cholinesterase activity (IC₅₀, 50.33 ± 0.87), though its glycosides (1, 2 and 3) were less active. HPLC analysis demonstrated that the three compounds were contained in the MeOH extract in the order of compounds 2 (12.63 mg/g extract) > 3 (3.10 mg/g) > 1 (2.92 mg/g).     

A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the roots of Juglans mandshurica and their anti-inflammatory activities

A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside, (2S,3S,5S)-2,3-dihydroxy-5-O-β-d-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptane (2), together with three known compounds, rhoiptelol C (3), rhoiptelol B (4) and 3′,4″-epoxy-2-O-β-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7-(3-methoxyphenyl)heptan-3-one (5) were isolated from the roots of Juglans mandshurica (Juglandaceae). The structures of compounds 1 and 2 were identified based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Compounds 1–5 were assayed for their inhibitory effects on the production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.     

A novel dimeric flavonol glycoside from Cynanchum acutum subsp. sibiricum

A novel dimeric flavonol glycoside, Cynanflavoside A (1), together with six analogues, kaempferol-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (2), quercetin-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (3), kaempferol-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside (4), quercetin-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside (5), kaempferol-3-O-β-D-glucopyranosyl-7-O-α-L-rhamnopyranoside (6), and quercetin-3-O-galactoside (7) were isolated from the n-butyl alcohol extract of Cynanchum acutum subsp. sibiricum. Their structures were determined spectroscopically and compared with previously reported spectral data. All compounds were evaluated for their anti-complementary activity in vitro, and only compound 5 exhibited anti-complement effects with CH₅₀ value of 0.33 mM.     

Phenolic compounds from the aerial parts of Clematis viticella L. and their in vitro anti-inflammatory activities*

Phytochemical investigations on the EtOH extract of Clematis viticella led to the isolation of six flavonoid glycosides, isoorientin (1), isoorientin 3′-O-methyl ether (2), quercetin 7-O-α-L-rhamnopyranoside (3), quercetin 3,7-di-O-α-L-rhamnopyranoside (4), manghaslin (5) and chrysoeriol 7-O-β-D-glucopyranoside (6), one phenylethanol derivative, hydroxytyrosol (7), along with three phenolic acids, caffeic acid (8), (E)-p-coumaric acid (9) and p-hydroxybenzoic acid (10). The structures of the isolates were elucidated on the basis of NMR and HR-MS data. All compounds were isolated from C. viticella for the first time. Compounds 7 and 8 showed significant anti-inflammatory activity at 100 μM by reducing the release of NO in LPS-stimulated macrophages comparable to positive control indomethacin. Compounds 3 and 7 exhibited anti-inflammatory activity through lowering the levels of TNF-α while 1, 3 and 5 decreased the levels of neopterin better than the positive controls.     

Glycosides of ursane-type triterpenoid,benzophenone, and iridoid from Vangueria agrestis (Fadogia agrestis) and their anti-infective activities

Abstract

Four ursane-type triterpenoid glycosides (1-4), two benzophenone glycosides (5 and 6), and one iridoid glucoside (7) were isolated and characterized from the dried roots of Vangueria agrestis. Compounds 1 (3-O-[α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl]pomolic acid 28-O-β-D-glucopyranosyl ester) and 5 (2-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyl]-6,4′-dihydroxy-4-methoxy benzophenone) were found to be new metabolites. The identity of all compounds has been accomplished, primarily, based on 1 D and 2 D NMR and HRESMS analysis. Compounds 6 and 2, showed inhibitory effect against Trypanosoma brucei with IC₅₀ 22.3 µM for 6 and IC₅₀ 11.1 µM, IC₉₀ 12.3 µM for 2.     

New flavonoid glycosides and other chemical constituents from Clerodendrum phlomidis leaves: isolation and characterisation

Phytochemical investigation of the plant Clerodendrum phlomidis Linn. F. (Lamiaceae) has now led to the isolation of two new flavonoid glycosides (1, 2) together with six known compounds identified as pectolinaringenin (3), pectolinaringenin-7-O-β-d-glucopyranoside (4), 24β-ethylcholesta-5,22E,25-triene-3β-ol (5), 24β-ethylcholesta-5,22E,25-triene-3β-O-β-D-glucopyranoside (6), (2S,3S,4R,10E)-2-[(2′R)-2′-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol (7) and andrographolide (8) mainly by spectroscopic analysis. Compounds 4 and 6–8 are reported for the first time from C. phlomidis.     

Rauvolfianine,a new antimycobacterial glyceroglycolipid and other constituents from Rauvolfia caffra. Sond (Apocynaceae)

The chemical investigation of the extract of the dried leaves of Rauvolfia caffra (Sond) (synonym Rauvolfia macrophylla) (Apocynaceae) led to isolation of a new glycoside derivative, rauvolfianine (1) as well as six known compounds: oleanolic acid (2), sitosterol-3-O-β-D-glucopyranoside (3), betulinic acid (4), vellosimine (5), sarpagine (6) and D-fructofuranosyl-β-(2→1)-α-D-glucopyranoside (7). Compounds 1, 2, 3, 4 and 7 were evaluated for antitubercular activity. Compounds 1 and 2 were the most active (MIC = 7.8125 and 31.25 μg/mL) towards the Isoniazid resistant strain of Mycobacterium tuberculosis AC45. Their structures and relative stereochemistry were elucidated by spectroscopic methods.     

A new C-glycosyl flavone and a new neolignan glycoside from Passiflora edulis Sims peel

A new C-glycosyl flavone, Chrysin-8-C-(2″-O-β-6-deoxy-glucopyranosyl)-β-D-glucopyranoside (1), a new neolignan glycoside, citrusin G (2), as well as 15 known compounds (3–17) were isolated from the peel of Passiflora edulis Sims. The structure determinations were primarily based on comprehensive spectroscopic analyses, and the absolute configuration of 2 were unequivocally determined by the CD experiment and chemical transformation. Compound 1 represents the rare examples of the flavonoid featuring a deoxy glucose sugar moiety. Compounds 5, 7 and 9 exhibited moderate inhibitory effects on nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells, with IC₅₀ values of 34.92, 16.12 and 26.67 μM, respectively.     

Two new flavonol glycosides from Dimocarpus longan leaves

From the extracts of Dimocarpus longan Lour leaves, 2 unusual flavonol glycosides, quercetin 3-O-(3″-O-2?-methyl-2?-hydroxylethyl)-β-d-xyloside (1) and quercetin 3-O-(3″-O-2?-methyl-2?-hydroxylethyl)-α-l-rhamnopyranoside (2), as well as 10 known compounds including 2 flavonol glycosides, afzelin (3) and kaempferol-3-O-α-l-rhamnopyranoside (4), 2 flavans, ( ? )-epicatechin (5) and proanthocyanidin A-2 (6), 3 triterpenoids, friedelin (7), epifriedelanol (8) and β-amyrin (9), a peptide, N-benzoylphenylalanyl-N-benzoylphenylalaninate (10), and 2 sterols, β-sitosterol (11) and daucosterol (12) were isolated and identified by using combination of mass spectrometry and various 1D and 2D NMR techniques. This is the first report of flavonoid glycosides possessing a 2-methyl-2-hydroxylethoxyl group in sugar moiety from D. longan.     

Three new flavonoid glycosides from Smilax glabra and their anti-inflammatory activity

Three new flavonoid glycosides, 2(S)-5-hydroxy-6,8-dimethoxyflavonone-7-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (1), 5-hydroxy-3,8-dimethoxyflavone-7-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (2) and 3,7-dihydroxy-8-methoxyflavone-6-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (3), together with five known flavonoids (4–8) were isolated from the roots of Smilax glabra Roxb. Their structures were elucidated on the basis of chemical and spectral evidence, as well as by comparison with literature data. Three new flavonoids were subjected to evaluate anti-inflammatory activity. Compounds 1–3 inhibited the NF κB induction by 32.2, 55.8 and 61.7%, respectively.     

Microbial transformation of quercetin and its prenylated derivatives

The microbial transformation studies of 7-O-prenylquercetin (1), 4′-O-prenylquercetin (2) and quercetin (3) were investigated with 20 different microbial strains to discover new metabolites. It was revealed that the fungus Mucor hiemalis was the most appropriate micro-organism which was capable of transforming these flavonoids. Structures of the three new (4–6) and one known (7) metabolites were elucidated as 7-O-prenylquercetin 3-O-β-D-glucopyranoside (4), 4′-O-prenylquercetin 3-O-β-D-glucopyranoside (5), 4′-O-prenylquercetin 3′-O-β-D-glucopyranoside (6) and quercetin 5-O-β-D-glucopyranoside (7) by the spectroscopic methods.     

New neolignan glycosides and a new cerebroside from <Emphasis Type="Italic">Symplocos caudata</Emphasis>

A phytochemical investigation of the roots of Symplocos caudata Wall (Symplocaceae) resulted in the isolation and characterization of two optical isomers of a neolignan glycoside (1) and a new cerebroside (2). Their structures were elucidated as (7R,8S)-erythro-7,9,9'-trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-4-O-β-D-glucopyranoside, (7S,8R)-erythro-7,9,9'-trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-4-O-β-Dglucopyranoside (1), and 1-O-β-D-glucopyranosyl-(2S,3S,4R,8Z,12E)-2-N-[(2'R)-2'-hydroxyheptacosanoyl]-8,12-docosadiene-1,3,4-triol (2), respectively, on the basis of spectroscopic data (1D and 2D NMR, MS and CD).     

Syntheses of Methyl 2-O-, 3-O- and 6-O-(2′-Hydroxypropyl)-α-D-Glucopyranosides 1

Abstract

Methyl 6-O-, 3-O- and 2-O-(2′-hydroxypropyl)-α-D-glucopyranosides (4,8, and 12) were synthesized starting from methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside (1), methyl 4,6-O-benzylidene-α-D-glucopyranoside (5), and methyl 3-O-benzyl-4,6-O-benzylidene-D-glucopyranoside (9), respectively. Overall yields were 88%, 6% and 26% of 4, 8 and 12, respectively, with the 2-ether (12) being crystalline and the 3-ether (8) a single diastereomer.

     

A new flavonol derivative from <Emphasis Type="Italic">Fagopyrum dibotrys</Emphasis>

A new flavonol derivative 3, 8-dihydroxy-10-methoxy-5-H-isochromeno[4, 3-b]chromen-7-one (1) together with four known compounds, glutinone (2), luteolin (3), acacetin 7-O-α-L-rhamnopyranosyl- (1→6)-β-D-glucopyranoside (4), and rutin (5) were isolated from the dried roots of Fagopyrum dibotrys. Their structures were determined by UV, IR, MS, ¹H, and ¹³C NMR spectroscopic analysis, including 2D NMR. Published in Khimiya Prirodnykh Soedinenii, No. 6, pp. 567–568, November–December, 2008.     

Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for the Shigella flexneri Serotype 2a O-Antigen

ABSTRACT

The stereocontrolled synthesis of methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (EC, 1), methyl α-L-rhamnopyranosyl-(1→3)-[α-D-glucopyranosyl-(1→4)]-α-L-rhamnopyranoside (B(E)C, 3) and methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyl-α-L-rhamnopyranoside (11) and 8 afforded the fully protected αE-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding βE-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding βE-disaccharide, namely, methyl β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (βEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the αE and βE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required αE-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-(1→4)-2,3-di-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.     

Triterpene Glycosides from Cussonia paniculata. I. Isolation and Structure Determination of Glycosides A, B1, B2, C, D, G2, H1, and H2 from Leaves of Cussonia paniculata

The 3-O-β-D-glucopyranoside of β-sitosterol (1) and the known triterpene glycosides 3-O-α-L-arabinopyranosides of oleanolic (2a) and ursolic (2b) acids and hederagenin (3), 3-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosideofoleanolic acid (4), 3-O-α-L-arabinopyranosyl-28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosides of oleanolic (5a) and ursolic (5b) acids and the newglycoside 28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside of 23-hydroxyursolic acid (6) were isolated from leaves of Cussonia paniculata (Araliaceae). Their structures were established using chemical methods and NMR spectroscopy.__________Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 160–163, March–April, 2005.     

Linear Synthesis of The Methyl Glycosides of Tri-, Tetra-, and Pentasaccharide Fragments of The Shigella Flexneri Serotype 5A O-Antigen

ABSTRACT

The stepwise synthesis of methyl α-D-glucopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (EBC-OMe, 1), methyl α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (A(E)BC-OMe, 2), and methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranoside (DA(E)BC-OMe, 3) is described. Compounds 1, 2 and 3 constitute the methyl glycosides of fragments of the O-specific polysaccharide of Shigella flexneri serotype 5a. Methyl 2,4-di-O-benzoyl-α-L-rhamnopyranosyl-(1→3)-2,4-di-O-benzoyl-α-L-rhamnopyranoside was an appropriate BC precursor for the synthesis of 1. For the synthesis of the branched targets 2 and 3, a benzyl group was best suited at position 2 of rhamnose C. Thus, methyl 4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside was the key intermediate to the BC portion. In all cases, 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride was a convenient E precursor, when used in combination with titanium tetrafluoride. All along, attention was paid to steric hindrance as a factor of major impact on the condensation steps outcome. Therefore, based on previous experience, 2-O-acetyl-3,4-di-O-allyl-α-L-rhamnopyranosyl trichloroacetimidate and 3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-α-D-glucopyranosyl trichloroacetimidate were used as donors. Both suited all requirements when used as key precursors for residues A and D in the synthesis of 3, respectively.     

Annelation of drotaverine by <Emphasis Type="Italic">p</Emphasis>-quinones to form hydroxyindolo- and hydroxybenzindoloisoquinoline derivatives

1-(3, 4-Diethoxybenzyl)-6, 7-diethoxy-3, 4-dihydroisoquinoline (drotaverine, 1a) reacts with p-benzoquinone (2) and p-naphthoquinone (3) in nitromethane or during fusion to give 5-(3, 4-diethoxyphenyl)-7, 8-diethoxy-3-hydroxy-5a, 10, 11, 12-tetrahydroindolo[2, 1-a]isoquinoline (4) and 7-(3, 4-diethoxyphenyl)-9, 10-diethoxy-5-hydroxy-7a, 12, 13, 14-tetrahydrobenz[g]indolo[2, 1-a]isoquinoline (5), respectively. Compounds 4 and 5 are smoothly alkylated at the oxygen atom in the presence of bases. The structure of one alkylation product, viz., 3-allyloxy-5-(3, 4-diethoxyphenyl)-7, 8-diethoxy-5a, 10, 11, 12-tetrahydroindolo[2, 1-a]isoquinoline, was established by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 761–769, March, 2005.     

Two new noroleanane-type triterpenoid saponins from the stems of Stauntonia chinensis

Two new noroleanane-type triterpenoid saponins, 3β,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-β-L-fucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranoside (1) and 3β,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-β-D-glucopyranosyl-(1→2)-[α-L-arabinopyranosyl-(1→3)]-β-D-glucopyranoside (2) were isolated from the stems of Stauntonia chinensis DC., together with three known compounds, brachyantheraoside B₂ (3), eupteleasaponin Ⅷ (4) and fargoside B (5). Their structures were elucidated by spectroscopic and chemical methods. The cytotoxic activities of compounds 1 and 2 were evaluated against five human tumor cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780). Compounds 1 and 2 showed moderate cytotoxic activities toward the tested cell lines with IC₅₀ values ranging from 12.71 to 32.04 μM.