Concise total synthesis of flavone C-glycoside having potent anti-inflammatory activity

The total synthesis of anti-inflammatory active flavone C-glycoside isolated from oolong tea extract is achieved. Introducing a C-glucosyl moiety to an aryl system and constructing a fused tetracyclic ring characteristic to this natural product were conducted based on the O-to-C rearrangement of sugar moiety and the successive intramolecular Mitsunobu reaction, respectively. This concise and efficient synthetic pathway is applicable to the large-scale synthesis of target flavone and for constructing a large library of related compounds.     

Synthesis of dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones bearing a sugar moiety

The synthesis of a series of dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones, structurally related to the G2 checkpoint inhibitor granulatimide and bearing a sugar moiety, is described. Substitutions were carried out at the 6-position of the glycosyl unit to lead to an amino substituent as observed in many biologically active compounds such as anthracyclins or staurosporines.     

Molecular recognition by a novel boronate-containing CTG derivative for hydroxyanthraquinones

C₃-functionalized cyclotriguaiacylene (CTG) derivatives were employed in the development of highly selective recognition compounds due to their unique molecular structures. Here, a novel C₃-functionalized CTG containing boronate (PPB-CTG) was synthesized and its molecular recognition ability for hydroxyanthraquinones was investigated by fluorescence spectroscopy. The addition of the synthesized PPB-CTG led to a large increase in the fluorescence intensity of only alizarin and not 1-hydroxyanthraquinone, 2-hydroxyanthraquinone nor quinizarin. It was, thus, suggested that the cyclotriveratrylene (CTV) structure plays an important role in the recognition ability toward alizarin since the mono-phenyl boronate compound (m-TPBAP) showed poor fluorescence properties toward alizarin. Moreover, it was found that the 1:1 mixture of PPB-CTG and alizarin was effective as a fluorescence-enhanced probe toward fluoride ions.     

Synthesis and chromatographic study of methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d-ribofuranoside

The synthesis of two riboside-containing arsenic compounds, methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d- ribofuranoside is presented in this paper. Intermediates and final products of the synthesis were examined by gas chromatography and thin layer chromatography. The purity of the products was assessed by NMR spectroscopy. Trimethylsilylation was used to volatilise sugar compounds and thus use of the costly HPLC–MS technique was avoided. The results affirmed the presence of tautomers in case of arsenosugars.     

Arabinofuranose disaccharide analogs as inhibitors of Mycobacterium tuberculosis

Several octyl 5-O-(α-d-arabinofuranosyl)-α-d-arabinofuranoside disaccharide analogs substituted at the 5-position of the non-reducing end sugar were synthesized and tested in vitro against Mycobacterium tuberculosis (M.tb.), Mycobacterium avium complex (MAC) as well as in a cell free assay system for arabinosyltransferase acceptor/inhibitor activity. A few compounds showed interesting inhibitory activity in the cell free assay as well as against the whole microorganism in vitro.     

Glucose and fructose levels on grape skin: interference in Lobesia botrana behaviour

The vineyard produces one of the most important crops in Portugal and is affected by various pests, such as the Lobesia botrana moth, which can be attracted chemically by compounds on the grape skin.In this study, the sugar contents (glucose and fructose) on grape skin were analysed for five Portuguese Vitis vinifera grape varieties and compared in grape juice and whole grapes. Samples were harvested in July, August and September of 2001 and 2002.The quantification was attained employing a new methodology, which comprised the preparation of a methanol solution to extract the compounds from the grape skin and further chromatographic analyses by liquid chromatography (LC) with refractive index (RI) detection. The samples designated by whole grapes were homogenised, centrifuged and filtrated, while the juice was obtained by crushing and filtration.Grape skin has shown higher levels of glucose than fructose, but both compounds increased from green berry (July) to veraison (August) and had a slight decrease from veraison to harvest (September).As expected, the glucose and fructose contents (total sugar) were higher in the whole grape than in the juice and much higher than in the grape skin itself. For Loureiro and Trajadura varieties, the levels of both sugars on grape skin were very similar. This resemblance strengthened the statement of the decisive role of this parameter in female L. botrana oviposition behaviour.     

The substrate specificity of a glucoamylase with steroidal saponin-rhamnosidase activity from Curvularia lunata

In previous work, we studied and reported that an enzyme from Curvularia lunata 3.4381 had the novel specificity to hydrolyze the terminal rhamnosyl at C-3 position of steroidal saponin and obtained four transformed products; the enzyme was purified and ascertained as glucoamylase (EC 3.2.1.3 GA). In this work, the enzyme exhibiting steroidal saponin-rhamnosidase activity was systematically studied on 21 steroidal saponins and 6 ginsenosides. The results showed that the α-1,2-linked end-rhamnosyl residues at C-3 position of steroidal saponins could be hydrolyzed to corresponding secondary steroidal saponins, among which 18 compounds were isolated and identified, including 3 new secondary compounds. For the furostanosides having glucosyl residues at the C-26 position, hydrolysis occurred first at end-rhamnosyl at C-3 position to produce secondary furostanosides. The reaction of hydrolyzing glucosyl at C-26 position depended considerably on longer reaction times yielding the corresponding secondary spirostanosides (without rhamnosyl and glucosyl residues). The enzyme had the strict specificity for the terminal α-1,2-linked rhamnosyl residues of linear chain, or the terminal α-1,2-linked rhamnosyl residues with branched chain of 1,4-linked glycosyl residues of sugar chain at C-3 position of steroidal saponins, it was not specific for different aglycones, different glycons, and the number of glycon of sugar chain of steroidal saponin. The end-rhamnosyl of ginsenosides and p-nitrophenyl-α-l-rhamnopyranoside (pNPR) could not be hydrolyzed by the enzyme from C. lunata.     

Identification of polyoxypregnane glycosides from the stems of Marsdenia tenacissima by high-performance liquid chromatography/tandem mass spectrometry

A facile method based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC/(+)ESI-MSⁿ) has been established for the analysis of polyoxypregnane glycosides in the stems of Marsdenia tenacissima. The data reveals the ability of MSⁿ in the structural elucidation of polyoxypregnane glycosides including the nature of the polyoxypregnane core, the kinds of the substituents and the types of sugar residues. Offline Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is also performed to assign accurate elemental compositions. In this study, eighteen polyoxypregnane glycosides have been investigated. Among these components, five compounds are unambiguously identified as Marsdenoside K, Tencissoside A, B, C and D; two compounds are established as novel compounds based on mass spectral data; and the other eleven compound's structures are tentatively proposed. Furthermore, breakdown curves are constructed to distinguish five pairs of isomers among these eighteen compounds. As far as our knowledge, this is the first report on identification of polyoxypregnane glycosides in the stems of M. tenacissima by HPLC/ESI-MSⁿ directly, which could save time and material consuming efforts in traditional phytochemistry analyses.     

Biopreparation of an anti-inflammatory agent,diarctigenin, from arctiin isolated from Arctium lappa by Rhizoctonia solani AG-4

In the preliminary screening for the plant-derived pesticides against Rhizoctonia solani Kühn AG-4 (RS AG-4), the indicator compounds arctiin (1) and arctigenin (2) in methanol extracts of Arctium lappa L. were consumed and transformed to other compounds. Thus, in the present study RS AG-4 was used as a biocatalyst and the biotransformation of arctiin (1) was investigated. Conversion of arctiin (1) to arctigenin (2) was achieved by the enzymatic hydrolysis of sugar moiety. In addition, an anti-inflammatory lignan dimer reported from the Arctium species, diarctigenin (3) was afforded in good yields. The HPLC monitoring of the biotransformation process indicated the possible mechanism. It would be an excellent method to produce a large scale of diarctigenin (3) for the successive medicinal examinations.     

Decomplexing madder lakes using oxalic acid: A novel method coupled with microwave or ultrasound processes

The aim of the present study was to establish a mild extraction and universal method to characterize madder lakes of Rubia tinctorum by liquid chromatography coupled with a photodiode array detector . To analyze the lakes, anthraquinone molecules must be decomplexed of metal links. To this end, two processes, one ultrasound and the other microwave, were improved in association with two solutions, an oxalic acid solution (0.5 M in MeOH/H₂O 50/50) and an acetic acid buffer solution (1 M). First, the decomplexation of an alizarin experimental lake was optimized in comparison with a reference method using a strong acid. The microwave process used oxalic acid and increased the decomplexation yield of alizarin (71%) compared with the reference method (31%). Second, different madder experimental lakes, which were prepared using different metal salts, were decomplexed. The obtained results suggest that the use of microwave associated with oxalic acid solution is the most universal method providing a decomplexation of anthraquinones from lakes without hydrolysis of glycosidic compounds occurring.     

Bioactive pregnane-type steroids from the soft coral Scleronephthya gracillimum

Nine new steroids, sclerosteroids A-I (1, 5, 6, 8-13), along with 18 known metabolites (2-4, 7, 14-27), were isolated from the soft coral Scleronephthya gracillimum. These structures were elucidated on the basis of detailed spectroscopic analysis. The absolute configurations of sugar moieties in steroidal glycosides 10-13 were determined by HPLC analysis of the o-tolylthiocarbamate derivatives of the liberated sugars from hydrolysis of these steroidal giycosides. Cytotoxic and anti-inflammatory activities of these compounds were measured in vitro.     

Voltammetric sensing of sugar by an electrode covered with wheat germ agglutinin/chitin film

The binding between wheat germ agglutinin (WGA) and N-acetylglucosamine at the electrode covered with chitin film was investigated with voltammetry. Chitin, β-1,4-poly-N-acetylglucosamine, is one of the biolpolymers which have a high biocompatibility. WGA is immobilized to the surface of chitin film by the affinity of WGA to N-acetylglucosamine residue of chitin. To investigate the binding event of WGA on the chitin modified electrode, N-acetylglucosamine labeled with an electroactive compound was prepared. The binding causes the changes in the electrode response of labeled sugar. The peak current of labeled sugar decreased due to the specific binding with WGA on the chitin film modified at the electrode. N-Acetylglucosamine was successfully determined by using the competitive reaction with labeled sugar to WGA on the chitin film electrode.     

Anomeric spiroannelated 1,4-diazepine 2,5-diones from furano exo-glycals: towards a new class of spironucleosides

The first synthesis of 1,4-diazepine 2,5-dione peptides containing a β-amino acid in which the β carbon is also the anomeric carbon of a furanoid sugar is described. These new anomeric spirosugars obtained with a stereoselective control in the d-gulo, d-manno, d-allo and d-ribo series can be regarded as the first members of a new class of spironucleosides. In the course of our study, two symmetrical tetrameric cyclopeptides comprising two identical sugar β-amino acid and α-amino acid residues were also isolated, these structures could be of interest as new potential host molecules.     

C-Glycopyranosyl-1,4-benzoquinones and -hydroquinones opening access to C-glycosylated analogs of vitamin E

2-(Per-O-acetyl-β-d-glycopyranosyl)-1,4-dimethoxybenzenes led to C-glycosyl-hydroquinones suitable for preparing C-glycosylated analogs of vitamin E, having the sugar moiety free or acetylated.     

Proanthocyanidin glycosides from the leaves of Quercus ilex L. (Fagaceae)

From the polar extracts of the leaves of Quercus ilex L., two new proanthocyanidin glycosides, namely afzelechin-(4α→8)-catechin-3-O-β-glucopyranoside (1) and afzelechin-(4α→8)-catechin-3-O-α-rhamnopyranoside (2), were isolated in addition to catechin (3), proanthocyanidin B₃ (4), prodelphinidin C (5), dehydrodicatechin A (6), quercetin (7) and six known flavonol glucosides with their acylated derivatives (8-13) and ellagic acid (14). The structures of all isolated compounds were established by spectroscopic means, mainly 1D and 2D NMR, as well as LC/MS and HR-MS spectrometric analyses. The absolute configuration of compound 1 was determined by CD measurements. The proanthocyanidin glycosides are especially interesting, as they possess the sugar in the upper unit of the dimer, which is rare for this type of compounds.     

Cytosporones O, P and Q from an endophytic Cytospora sp.

Cytosporones O, P and Q, together with the known compounds cytosporones B, C, D, E and dothiorelones A, B, C, and H were isolated from the ascomycete fungus Cytospora sp. during a chemotaxonomic study of fungal endophytes belonging to the related genera Cytospora and Phomopsis from Brazil. The structures were determined by NMR spectroscopy and mass spectrometry. With exception of cytosporones D, E, Q, and dothiorelone B, all compounds were consistently detected in the metabolite profiles of eight Cytospora isolates investigated; and were also produced by a distinct chemotype of Phomopsis.     

Emervaridione and varioxiranediol, two new metabolites from the endophytic fungus, Emericella variecolor

Two new compounds, emervaridione and varioxiranediol, together with the three known compounds, stellatic acid, ergosterol and dihydroterrein, were isolated from the endophytic fungus, Emericella variecolor. The structures of emervaridione and varioxiranediol were established from spectroscopic and X-ray crystallographic analysis.     

New constituents from Mikania laevigata Shultz Bip. ex Baker

A new phenylpropanoid and two new diterpenes were isolated from the leaves of the plant Mikania laevigata Shultz Bip. ex Baker. The structures of these compounds were established by 1D- and 2D-nuclear magnetic resonance spectroscopic techniques and mass spectrometry data. Taraxerol, lupeol, coumarin, syringaldehyde, trans-melilotoside, cis-melilotoside, adenosine, patuletin 3-O-β-d-glucopyranoside, kaempferol 3-O-β-d-glucopyranoside, quercetin 3-O-β-d-glucopyranoside, methyl 3,5-di-O-caffeoyl quinate, and 3,3′,5-trihydroxy-4′,6,7-trimethoxyflavone were isolated too. In addition, the compounds dihydrocoumarin, spathulenol, caryophyllene oxide, kaurenoic acid, beyerenoic acid, and lupeol acetate were identified by GC-MS.     

Synthesis of a C3-symmetric macrocycle with alternating sugar amino acid and tyrosine residues

A C₃-symmetric macrocycle with alternating sugar amino acid and tyrosine residues was synthesized in seven steps from tyrosine tert-butyl ester and a sugar amino acid precursor derived from D-glucosamine. An Fmoc-protected D-glucosamine derivative was oxidized at C-6 to give the sugar amino acid, which was immediately coupled to tyrosine tert-butyl ester to produce an orthogonally protected building block. This building block was subsequently elongated to the trimer via the dimer, and finally cyclized to give the C₃-symmetric macrocycle.     

Rapid structural determination of modified pregnane glycosides from Cynanchum forrestii by liquid chromatography-diode-array detection/electrospray ionization multi-stage tandem mass spectrometry

The fragmentation behaviors of the two types of modified pregnane glycosides from Cynanchum forrestii were investigated by positive ion electrospray ionization multi-stage tandem mass spectrometry equipped with an ion trap analyzer. The spectral data further illuminated the predominance of ESI-MSⁿ technique on the identification of pregnane glycosides, especially of two sorts of modified pregnane glycosides with aglycone skeletons of 13,14:14,15-disecopregnane-type and 14,15-secopregnane-type, which differed in the presence of the characteristic [M−46+Na]⁺ ion. For sugar residues, the fragment ions were analyzed and some possible fragmentation pathways were proposed, especially for 3-demethyl-2-deoxythevetose, the glycosidic cleavage reaction was easier to occur than those of other sugar units in its moiety. The natures and differences of the pregnane cores, and the types and linked sequences of sugar residues were illustrated. According to these conclusions, eight new pregnane glycosides in the fraction of Cynanchum forrestii were structurally elucidated by HPLC/HRMS and HPLC-DAD/ESI-MSⁿ techniques. Results of the present studies can benefit the rapid identification and structural determination of analogous constituents in crude plant extracts.