Chemical constituents from Potentilla fragarioides L

Phytochemical investigation on Potentilla fragarioides L. has led to the identification of twelve compounds including β-sitosterol (1), β-daucosterol (2), ursolic acid (3), pomolic acid (4), swinhoeic acid (5), (1-p-hydroxy-cis-cinnamoyl)cinnamic acid (6), trans-caffeoylisocitric acid (7), trans-caffeic acid (8), quercetin (9), quercetin-3-O-β-D-glucuronide (10), (+)-catechin (11) and 3-O-methylellagic acid-4′-O-ɑ-L-rhamnopyranoside (12). Among them, compounds 4–7 were first identified from the genus Potentilla. And the other compounds except compounds 8 and 11 were found in Potentilla fragarioides for the first time. Chemotaxonomic significance of these compounds was discussed.     

Phenylpropanoid glycosides from the roots of Jasminum giraldii

As part of our ongoing research in medicinal herbs of Qinba Mountains in China, the plant Jasminum giraldii was chemically investigated. Four new phenylpropanoid glycosides, 9-O-(E-cinnamoyl)-coniferin (1), 6′-O-(E-cinnamoyl)-coniferin (2), 6′-O-(E-cinnamoyl)-syringin (3) and 2′-O-(E-cinnamoyl)-syringin (4), together with two known phenylpropanoid glucosides, coniferin (5) and ethylsyringin (6) were obtained from the roots of Jasminum girialdii. The structures of these compounds have been characterized according to spectral evidences and named on basis of their biosynthetic pathway. In addition, in vitro cytotoxic activities of these compounds were evaluated, however, none of these compounds showed cytotoxicity.     

Chemical constituents from Oncocalyx glabratus and their biological activities

Chemical investigation of the aerial parts of Oncocalyx glabratus resulted in the isolation of three new flavan derivatives, 5,3′,4′-trihydroxyflavan 7-O-gallate (1), 5,4′-dihydroxyflavan 7-3′-O-digallate (2) and 5,3′-dihydroxyflavan 7-4′-O-digallate (3), named oncoglabrinol A, B and C, respectively, together with four known flavonols, (+)-catechin (4), (+)-catechin-7-O-gallate (5), catechin-7-4′-O-digallate (6A) and catechin-7-3′-O-digallate (6B). The structures of the compounds were established by 1D, 2D NMR and ESI-HRMS spectral analyses. The biological activity of the compounds was tested through a series of in vitro assays designed for determining cytotoxicity, antiviral activity against hepatitis B virus, and antidiabetic activity. All compounds were found non-toxic and showed moderate anti-HBV activity. Compounds 3 and 6 showed dual PPAR agonistic activity while others were not effective.     

Anthraquinone,anthrone and phenylpyrone components of Aloe nyeriensis var. kedongensis leaf exudate

The leaf exudate of Aloe nyeriensis var. kedongensis yielded six compounds which were identified on the basis of spectral data and inter-conversions as two groups of three allied compounds. These were (a) 4-methoxy-6(2′,4′-dihydroxy-6′- methylphenyl)-pyran-2-one, its 2′-O-β-D-glucopyranoside (aloenin) and the 2″-O-p-coumaroyl ester of aloenin, (b) the anthracene derivatives l,2,8-trihydroxy- 6-methylanthraquinone (nataloe-emodin), its 2-O-β-D-glucopyranosyl ester and the corresponding 10-C -β-D-glucopyranoside nataloin.     

New glycosides from the leaves and rattan stems of Schisandra chinensis

Two new glycosides, vanillic acid 4-O-β-d-(6′-O-(Z)-2′'-methylbut-2′'-enoate)glucopyranoside (1), p-methoxycarvacrol-6-O-β-d-glucopyranoside (2), along with two known analogues (3-4), were isolated from the leaves and rattan stems of Schisandra chinensis. The structures of these isolates were determined by UV, HRESIMS, 1D and 2D NMR spectral analyses.     

Regioselective acylation of several polyhydroxylated natural compounds by Candida antarctica lipase B

Regioselective acylation of four polyhydroxylated natural compounds, deacetyl asperulosidic acid (1), asperulosidic acid (2), puerarin (3) and resveratrol (4) by Candida antarctica Lipase B in the presence of various acyl donors (vinyl acetate, vinyl decanoate or vinyl cinnamoate) was studied. Compounds 1, 2 and 4 were regioselectively acetylated with vinyl acetate to afford products, 3′-O-acetyl-10-O-deacetylasperulosidic acid (1a), 3′,6′-O-diacetyl-10-O-deacetylasperulosidic acid (1b), 3′-O-acetylasperulosidic acid (2a), 3′,6′-O-diacetylasperulosidic acid (2b), 4′-O-acetylresveratrol (4a), respectively, with yields of 22 to 50%, while reactions with vinyl decanoate and vinyl cinnamoate were slow with lower yields. Compound 3 was readily acylated with all three acyl donors and quantitatively converted to products 6″-O-acetylpuerarin (3a), 6″-O-decanoylpuerarin (3b), 6″-O-cinnamoylpuerarin (3c), respectively. The structures of these acylated products were determined by spectroscopic methods (MS and NMR).     

Enzymatic synthesis of lactosylated and sialylated derivatives of epothilone A

Epothilone A is a derivative of 16-membered polyketide natural product, which has comparable chemotherapeutic effect like taxol. Introduction of sialic acids to these chemotherapeutic agents could generate interesting therapeutic glycoconjugates with significant effects in clinical studies. Since, most of the organisms biosynthesize sialic acids in their cell surface, they are key mediators in cellular events (cell-cell recognition, cell-matrix interactions). Interaction between such therapeutic sugar parts and cellular polysaccharides could generate interesting result in drugs like epothilone A. Based on this hypothesis, epothilone A glucoside (epothilone A 6-O-β-D-glucoside) was further decorated by conjugating enzymatically galactose followed by sialic acids to generate epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactoside i.e., lactosyl epothilone A (lac epoA) and two sialosides of epothilone A namely epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactopyranosyl 3″-O-α-N-acetyl neuraminic acid and epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactopyranosyl 6″-O-α-N-acetylneuraminic acid i.e., 3′sialyllactosyl epothilone A: 3′SL-epoA, and 6′sialyllactosyl epothilone A: 6′SL-epoA, respectively. These synthesized analogs were spectroscopically analyzed and elucidated, and biologically validated using HUVEC and HCT116 cancer cell lines.     

Three flavonoid glycosides containing acetylated allose from stachys recta

By means of ¹³C and ¹H NMR spectroscopy three flavone glycosides, obtained from Stachys recta, were identified as 7-O-(2″-O-6″′-O-acetyl-β-D-allopyranosyl-β-D-glucopyranosides) of 4′-O-methylisoscutellarein, isoscutellarein and 3′-hydroxy-4′-O-methylisoscutellarein. The latter two compounds are isolated for the first time. Only mannose and glucose have been reported previously as sugar components of flavonoids of the genus Stachys.     

New flavonoids from the fruits of Cornus mas,Cornaceae

One new β-hydroxychalcone, 4-acetoxy-5,2′,4′,6′,β-pentahydroxy-3-methoxychalcone (1), one new flavanone, 7,3′-dihydroxy-5,4′-dimethoxyflavanone (2) and seven known compounds, 2R, 3R-trans-aromadendrin (3), naringenin-7-O-methylether (4), myricetin (5), quercetin-3-O-rutinoside (6), ursolic acid (7), gallic acid (8) and d-glucose (9) were isolated from the methanolic fruit extract of Cornus mas L. (=Cornus mascula L.), Cornaceae. The structures of the new compounds were elucidated on the basis of extensive spectroscopic methods, including 2D NMR experiments and of known compounds by comparison of physical and spectral data with literature.     

Chemical constituents of Trilepisium madagascariense (Moraceae) and their antimicrobial activity

The chemical study of Trilepisium madagascariense has led to the isolation of two previously undescribed compounds, (+)-(2S)-7-hydroxy-3′,4′-dimethoxyflavan (trilepisflavan) and (E)-4-[3-(3,4-dihydroxyphenyl)prop-2-enoyloxy]-3-hydroxybenzoic acid (trilepisuimic acid), together with ten known compounds caffeic acid, catechin, erythrodiol-3-O-palmitate, 8-C-glucopyranosylapigenin, dihydrokaempferol, protocatechuic acid, 3′,7-dihydroxy-4′-methoxyflavan, isoliquiritigenin, luteolin and 1,3-dimethoxybenzene. Their structures were elucidated on the basis of spectroscopic evidence. Crude extracts, trilepisflavan, dihydrokaempferol and 8-C-glucopyranosylapigenin showed significant antimicrobial activity.     

A convenient synthesis of 6′-C-substituted β-maltose heptaacetates and of panose

Benzylidenation of β-maltose monohydrate with α,α-dimethoxytoluene in N,N-dimethylformamide in the presence of p-toluenesulfonic acid gave, in 70% yield, 4′,6′-O-benzylidenemaltose, which was acetylated to afford, 1,2,3,6,2′,3′-hexa-O-acetyl-4′,6′-O-benzylidene-β-maltose (4). Removal of the benzylidene group of 4 gave 1,2,3,6,2′,3′-hexa-O-acetyl-β-maltose (5), which was transformed into 1,2,3,6,2′,3′,4′-hepta-O-acetyl-6′-O-p-tolylsulfonyl-β-maltose (8). Several 6′-substituted β-maltose heptaacetates were synthesized by displacement reactions of 8 with various nucleophiles. Condensation of 5 with 2,3,4,6-tetra-O-benzyl-α-d-glucopyranosyl bromide, under catalysis by halide ion, followed by removal of protecting groups, furnished panose in good yield.     

Acetylated allose-containing flavonoid glucosides from Stachys anisochila

In continuation of our chemosystematic study of Stachys (Labiatae) we have isolated the previously reported isoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranoside] (1) and 3′-hydroxy-4′-O-methylisoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranoside] (4) and four new allose-containing flavonoid glycosides from S. anisochila. The new glycosides are hypolaetin 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranside] (6) as well as the three corresponding diacetyl analogues of 1, 4 and 6, isoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside], 3′-hydroxy-4′-O-methylisoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside] and hypolaetin 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside]. Extensive two-dimensional NMR studies (proton-carbon correlations, COSY experiments) allowed assignment of all ¹H NMR sugar signals and a correction of the ¹³C NMR signal assignments for C-2 and C-3 of the allose.     

Chromone acyl glucosides and an ayanin glucoside from Dasiphora parvifolia

Two new chromone acyl glucosides, 5-hydroxy-7-O-(6-O-p-cis-coumaroyl-β-D-glucopyranosyl)-chromone (1) and 5-hydroxy-7-O-(6-O-p-trans-coumaroyl-β-D-glucopyranosyl)-chromone (2), and a new flavonoid glucoside, ayanin 3′-O-β-D-glucopyranoside (3) were isolated from aerial parts of Dasiphora parvifolia, together with flavonoid glycosides (4–10), catechins (11, 12), and hydrolysable tannins (13, 14). The chemical structures of these compounds were elucidated on the basis of spectroscopic data. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and the hyaluronidase inhibitory activity of these compounds were evaluated.     

Tyrosinase inhibitory activity of three new glycosides from Breynia fruticosa

Two new flavanone glycoside derivatives and one new sulfur-containing spiroacetal glycoside, (2R, 3R)-3-acetyl-7-methoxy-(−)-epicatechin 5-O-(6-isobutanoyl)-β-d-glucopyranoside (1), (2R, 3R)-3-acetyl-7-methoxy-(−)-epicatechin 5-O-[6-(2-methylbutanoyl)]-β-d-glucopyranoside (2) and 4-[(carboxymethyl)thio]-5′-hydroxy-phyllaemblic acid O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranoside ester (3), along with twelve known flavonoids and one known sulfur-containing spiroacetal glycoside, were isolated from Breynia fruticosa. Their structures were elucidated by the use of extensive spectroscopic methods (UV, IR, HR-ESI-MS, 1D and 2D NMR, and CD). The in vitro inhibition of tyrosinase activity by all of these compounds was also evaluated, and we concluded that the flavanol-containing 5-O- and 7-O-sugar moieties possessed more potent effects than the other compounds examined herein.     

Synthesis and anti-CVB3 activity of 4-amino acid derivative substituted pyrimidine nucleoside analogues

Seven novel 4-amino acid derivative substituted pyrimidine nucleoside analogues were designed, synthesized, and tested for their anti-CVB3 activity. Initial biological studies indicated that among these 4-amino acid derivative substituted pyrimidine nucleoside analogues, 4-N-(2′-amino-glutaric acid-1′-methylester)-1-(2′- deoxy-2′-β-fluoro-4′-azido)-furanosyl-cytosine 2 exhibited the most potent anti-CVB activity (IC₅₀ = 9.3 μM). The cytotoxicity of these compounds has also been assessed. The toxicity of compound 2 was similar to that of ribavirin.     

Flavonoid diversification in different leaf compartments of Primula auricula (Primulaceae)

Populations of Primula auricula L. subsp. auricula from Austrian Alps were studied for flavonoid composition of both farinose exudates and tissue of leaves. The leaf exudate yielded Primula-type flavones, such as unsubstituted flavone and its derivatives, while tissue flavonoids largely consisted of flavonol 3-O-glycosides, based upon kaempferol (3, 4) and isorhamnetin (5–7). Kaempferol 3-O-(2″-O-β-xylopyranosyl-[6″-O-β-xylopyranosyl]-β-glucopyranoside) (3) and isorhamnetin 3-O-(2″-O-β-xylopyranosyl-[6″-O-β-xylopyranosyl]-β-glucopyranoside) (6) are newly reported as natural compounds. Remarkably, two Primula type flavones were also detected in tissues, namely 3′-hydroxyflavone 3′-O-β-glucoside (1) and 3′,4′-dihydroxyflavone 4′-O-β-glucoside (2), of which (1) is reported here for the first time as natural product. All structures were unambiguously identified by NMR and MS data. Earlier reports on the occurrence of 7,2′-dihydroxyflavone 7-O-glucoside (macrophylloside) in this species could not be confirmed. This structure was now shown to correspond to 3′,4′-dihydroxyflavone 4′-O-glucoside (2) by comparison of NMR data. Observed exudate variations might be specific for geographically separated populations. The structural diversification between tissue and exudate flavonoids is assumed to be indicative for different ecological roles in planta.     

New oleanane-type saponins: Leptocarposide B-D,from Ludwigia leptocarpa (Onagraceae)

Three new oleanane-type saponins, leptocarposide B-D (1–3), were isolated from the whole plant of Ludwigia leptocarpa (Nutt.) Hara, together with ten known compounds 4–13.The structures of these compounds were determined by interpretation of their spectral data, mainly HR-TOFESIMS, 1D-NMR (¹H, ¹³C) and 2D-NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY), and by comparison with the literature data. The structures of the new compounds were established as 28-O-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-[α-l-arabinopyranosyl-(1 → 3)]-4-O-(3′-hydroxybutanoyloxy-3-hydroxybutanoyloxy)-β-d-fucopyranosyl zanhic acid (1); 3-O-β-d-glucopyranosyl-28-O-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-4-O-(3′-hydroxybutanoyloxy-3-hydroxybutanoyloxy)-β-d-fucopyranosyl medicagenic acid (2); 3-O-β-d-glucopyranosyl-(1 → 4)-β-d-glucopyranosyl-28-O-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-[α-l- arabinopyranosyl-(1 → 3)]-4-O-(3′-hydroxybutanoyloxy-3-hydroxybutanoyloxy)-β-d-fucopyranosyl zanhic acid (3).     

Dihydrochalcone glucosides and antioxidant activity from the roots of Anneslea fragrans var. lanceolata

Bioassay-guided fractionation of the roots of Anneslea fragrans var. lanceolata led to the isolation of four dihydrochalcone glucosides, davidigenin-2′-O-(6″-O-4″′-hydroxybenzoyl)-β-glucoside (1), davidigenin-2′-O-(2″-O-4″′-hydroxybenzoyl)-β-glucoside (2), davidigenin-2′-O-(3″-O-4″′-hydroxybenzoyl)-β-glucoside (3), and davidigenin-2′-O-(6″-O-syringoyl)-β-glucoside (4), and 13 known compounds. The structures were identified by means of spectroscopic analysis. Davidigenin-2′-O-(6″-O-syringoyl)-β-glucoside (4), 1-O-3,4-dimethoxy-5-hydroxyphenyl-6-O-(3,5-di-O-methylgalloyl)-β-glucopyranoside (5), lyoniresinol (10), and syringic acid (13) showed ABTS [2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)] cation radical scavenging activity, with SC₅₀ values of 52.6 ± 5.5, 26.0 ± 0.7, 6.0 ± 0.2, and 27.5 ± 0.6 μg/mL in 20 min, respectively. Lyoniresinol (10), isofraxidin (12), and syringic acid (13) also showed DPPH [1,1-diphenyl-2-picrylhydrazyl] radical scavenging activity, with SC₅₀ values of 8.4 ± 1.8, 51.6 ± 2.2, and 4.3 ± 0.7 μg/mL in 30 min, respectively.     

Synthesis of 6-substituted uridines. synthesis of (R or S)-6-(3-amino-2-carboxypropyl)uridine

Addition of 5-bromo-2′,3′-O-isopropylidene-5′-O-trityluridine (2) in pyridine to an excess of 2-lithio-1,3-dithiane (3) in oxolane at 78° gave (6R)-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene -5′-O-trityluridine (4), (5S,6S)-5-bromo-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene-5′-O-trityluridine (5), and its (5R) isomer 6 in yields of 37, 35, and 10%, respectively. The structure of 4 was proved by Raney nickel desulphurization to (6S)-5,6-dihydro-2′,3′-O-isopropylidene-6-methyl-5′-O-trityluridine (7) and by acid hydrolysis to give D-ribose and (6R)-5,6-dihydro-6-(1,3-dithian-2-yl)uracil (9). Treatment of 4 with methyl iodide in aqueous acetone gave a 30&%; yield of (R,S)-5,6-dihydro-6-formyl-2′,3′-O-isopropylidene-5′-O-trityl-uridine (10), characterized as its semicarbazone 11. Both 5 and 6 gave 4 upon brief treatment with Raney nickel. Both 5 and 6 also gave 6-formyl-2′,3′-O-isopropylidene-5′- O-trityluridine (12) in ～41%; yield when treated with methyl iodide in aqueous acetone containin- 10%; dimethyl sulfoxide. A by-product, identified as the N-methyl derivative (13) of 12 was also formed in yields which varied with the amount of dimethyl sulfoxide used. Reduction of 12 with sodium borohydride, followed by deprotection, afforded 6-(hydroxymethyl)uridine (17), characterized by hydrolysis to the known 6-(hydroxymethyl)uracil (18). Knoevenagel condensation of a mixture of the aldehydes 12 and 13 with ethyl cyanoacetate yielded 38%; of E- (or Z-)6-[(2-cyano-2-ethoxycarbonyl)ethylidene]-2′,3′-O-isopropylidene-5′-O-trityluridine (19) and 10%; of its N-methyl derivative 20. Hydrogenation of 19 over platinum oxide in acetic anhydride followed by deprotection gave R (or S)-6-(3-amino-2-carboxypropyl)uridine (23).     

Microbial metabolism of prenylated apigenin derivatives by Mucor hiemalis

6-Prenylapigenin (1) and 8-prenylapegenin (2) were semi-synthesized from apigenin by nuclear prenylation. Morusin (3) was isolated from the root bark of Morus alba L. The microbial transformation studies of these three bioactive prenylated apigenin derivatives were performed using eighteen cell cultures in order to select microorganisms capable of transforming them. It was identified that Mucor hiemalis (KCTC 26779) showed the ability to metabolize the parent compounds (1–3) into three new (4–6) and one known (7) glucosylated derivatives with high efficiency. Their structures were established as 6-prenylapigenin 7-O-β-d-glucopyranoside (4), 8-prenylapigenin 7-O-β-d-glucopyranoside (5), morusin 5-O-β-d-glucopyranoside (6), and morusin 4′-O-β-d-glucopyranoside (7) by the spectroscopic methods.