Solution properties of an alpha-(1-->3)-D-glucan from Lentinus edodes and its sulfated derivatives

A water-insoluble alpha-(1-->3)-D-glucan (A) from Lentinus edodes was fractionated into 13 fractions in dimethyl sulfoxide containing 0.25 M lithium chloride (0.25 M LiCl-Me(2)SO). Five fractions were treated with sulfur trioxide-pyridine complex at 25 degrees C to synthesize water-soluble sulfated derivatives (S-A). The weight-average molecular weights, M(w), and intrinsic viscosities [eta], of the samples A and S-A were determined by multi-angler laser light scattering (MALLS), and viscosity. The M(w) dependence of [eta] and of the radius of gyration (z)(1/2), was found to be represented approximately by [eta]=4.9 x 10(-2) M(w)(0.67) (cm(3) g(-1)), and (z)(1/2)=4.8 x 10(-2) M(w)(0.54) (nm) for the alpha-glucan in 0.25 M LiCl-Me(2)SO in the M(w) range from 7.24 x 10(4) to 4.21 x 10(5), and by [eta]=6.8 x 10(-4) M(w) 1.06 (cm(3) g(-1)), and (z)(1/2)=9.4 x 10(-4) M(w)(0.92) (nm) for the sulfated alpha-glucan in aqueous 0.5 M NaCl in the M(w) range from 5.92 x 10(4) to 1.42 x 10(5) at 25 degrees C. The results indicate that the alpha-(1-->3)-D-glucan exists as a flexible chain in 0.25 M LiCl-Me(2)SO, and its sulfated derivative in 0.5 M NaCl aqueous has stiffer chains than the original. (13)C NMR indicated that intramolecular hydrogen bonding occurred in the sulfated alpha-glucan, causing the observed chain stiffness.     

Evaluation of sulfated Lentinus edodes alpha-(1-->3)-D-glucan as a potential antitumor agent

Alpha-glucan L-FV-II and beta-glucan L-FV-I were shown to co-exist in the extract of fruiting bodies of Lentinus edodes with aq. 5% NaOH/0.05% NaBH4 in previous work. Water-insoluble alpha-(1-->3)-D-glucan (L-FV-II) was treated with sulfur trioxide-pyridine complex at 25 degrees C to synthesize the water-soluble sulfated derivative SL-FV-II with a degree of substitution (DS) 1.1 in non-selective sulfation. The weight-average molecular weight (Mw) of sulfated glucan SL-FV-II is 57% of that of the original alpha-glucan L-FV-II. The alpha-glucan administered by gavaging at a dose of 50 mg/kg of body weight to BALB/C mice having implanted solid Sarcoma 180 was effective at an inhibition rate of 42%. In vitro experiments using human and murine tumor cell lines showed that SL-FV-II had antiproliferation activity at the concentration of 20 microg/mL towards four tumor cell lines. The sulfated alpha-(1-->3)-D-glucan had potent antiproliferation action (52%) on human MCF-7 breast carcinoma cells.     

Antitumor activities of O-sulfonated derivatives of (1-->3)-alpha-D-glucan from different Lentinus edodes

Four water-insoluble (1-->3)-alpha-D-glucans, coded L-II1, L-II2, L-II3 and L-II4, with different molecular weights were isolated from four kinds of fruiting bodies of Lentinus Edodes. The four alpha-D-glucans were O-sulfonated to obtain derivatives (SL-II) having degrees of substitution (DS) from 0.9 to 2.1 respectively. The structure of the samples was analyzed by infrared spectra, elemental analysis, and 13C NMR. The weight-average molecular weight (Mw), radii of gyration (z1/2) and intrinsic viscosity ([eta]) of the native alpha-D-glucans and O-sulfonated derivatives were measured by size-exclusion chromatography combined with laser light scattering (SEC-LLS), LLS, and viscometry in 0.2 M aqueous NaCl and in dimethyl sulfoxide (DMSO) containing 0.25 M LiCl at 25 degrees C respectively. The Mw values of the O-sulfonated derivatives were much lower than those of the native alpha-D-glucans. The experimental results indicate that the O-sulfonated derivatives are water-soluble and exist as an expanded flexible chain in aqueous solution owing to intramolecular hydrogen bonding or interaction between charge groups. The in vivo and in vitro antitumor activities of the native alpha-D-glucans and their O-sulfonated derivatives against solid tumor Sarcoma 180 cells were evaluated and compared. Interestingly, all of the O-sulfonated derivatives exhibited higher antitumor activities than those of the native glucans. The results reveal that the effect of O-sulfonation of the alpha-D-glucan on the improvement of their antitumor activities was considerable.     

Solution properties of antitumor sulfated derivative of alpha-(1-->3)-D-glucan from Ganoderma lucidum

Four fractions of a water-insoluble alpha-(1-->3)-D-glucan GL extracted from fruiting bodies of Ganoderma lucidum were dissolved in 0.25 M LiCl/DMSO, and then reacted with sulfur trioxide-pyridine complex at 80 degrees C to synthesize a series of water-soluble sulfated derivatives S-GL. The degree of substitution of DS was measured by using IR infrared spectra, elemental analysis, and 13C NMR to be 1.2-1.6 in the non-selective sulfation. Weight-average molecular weight Mw and intrinsic viscosity [eta] of the sulfated derivatives S-GL were measured by multi-angle laser light scattering and viscometry. The Mw value (2.4 x 10(4)) of sulfated glucan S-GL-1 was much lower than that (44.5 x 10(4)) of original alpha-(1-->3)-D-glucan GL-1. The Mark-Houwink equation and average value of characteristic ratio C(infinity) for the S-GL in 0.2 M NaCl aqueous solution at 25 degrees C were found to be: [eta] = 1.32 x 10(-3) Mw(1.06) (cm3 g(-1)) and 16, respectively, in the Mw range from 1.1 x 10(4) to 2.4 x 10(4). It indicated that the sulfated derivatives of the alpha-(1-->3)-D-glucan in the aqueous solution behave as an expanded chain, owing to intramolecular hydrogen bonding or interaction between charge groups. Interestingly, two sulfated derivatives synthesized from the alpha-(1-->3)-D-glucan and curdlan, a beta-(1-->3)-D-glucan, all had significant higher antitumor activity against Ehrlich ascites carcinoma (EAC) than the originals. The effect of expanded chains of the sulfated glucan in the aqueous solution on the improvement of the antitumor activity could not be negligible.     

Three exopolysaccharides of the beta-(1-->6)-D-glucan type and a beta-(1-->3;1-->6)-D-glucan produced by strains of Botryosphaeria rhodina isolated from rotting tropical fruit

Four exopolysaccharides (EPS) obtained from Botryosphaeria rhodina strains isolated from rotting tropical fruit (graviola, mango, pinha, and orange) grown on sucrose were purified on Sepharose CL-4B. Total acid hydrolysis of each EPS yielded only glucose. Data from methylation analysis and (13)C NMR spectroscopy indicated that the EPS from the graviola isolate consisted of a main chain of glucopyranosyl (1-->3) linkages substituted at O-6 as shown in the putative structure below: [carbohydrate structure: see text]. The EPS of the other fungal isolates consisted of a linear chain of (1-->6)-linked glucopyranosyl residues of the following structure: [carbohydrate structure: see text]. FTIR spectra showed one band at 891 cm(-1), and (13)C NMR spectroscopy showed that all glucosidic linkages were of the beta-configuration. Dye-inclusion studies with Congo Red indicated that each EPS existed in a triple-helix conformational state. beta-(1-->6)-d-Glucans produced as exocellular polysaccharides by fungi are uncommon.     

The conformation of alpha-(1-->4)-linked glucose oligomers from maltose to maltoheptaose and short-chain amylose in solution

The conformation of maltose-type oligomers in water and in dimethylsulfoxide (Me2SO) was studied using two-dimensional NMR spectra. In Me2SO all of the oligomers have a 1a-type conformation. In water, they tend to adopt the same conformation, but the oligomers are looser and more flexible than in Me2SO.     

The solubilization and biological activities of Aspergillus beta-(1 --> 3)-D-glucan

We have recently demonstrated that the cell wall beta-glucan of Candida albicans could be solubilized by sodium hypochlorite, followed by dimethylsulfoxide-extraction (NaClO-DMSO method). In this study, applying this method to Aspergillus spp., we prepared mycelial cell wall beta-glucan and examined its physical properties and immunotoxicological activity. The acetone-dried mycelia of Aspergillus spp. were oxidized by the NaClO-DMSO method. An analysis of (13)C NMR spectra revealed the preparations to be composed of alpha-(1 --> 3) and beta-(1 --> 3)-D-glucan. Also, the proportion of alpha-(1 --> 3) and beta-(1 --> 3)-D-glucan varied. Furthermore, a solubilized Aspergillus beta-glucan (ASBG) was prepared from OX-Asp by urea-autoclave treatment. ASBG showed limulus activity similar to Candida solubilized beta-glucan (CSBG), and there was little difference in the activity of ASBG between various Aspergillus spp. ASBG affected the production of IL-8 by human peripheral blood mononuclear cells (PBMC). ASBG should be useful for analyzing the clinical role of beta-glucan.     

Concise syntheses of arabinogalactans with beta-(1-->6)-linked galactopyranose backbones and alpha-(1-->3)- and alpha-(1-->2)-linked arabinofuranose side chains

4-methoxyphenyl glycosides of 2,3'-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl tetraose (16), 3',2'-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of beta-(1-->6)-linked D-galactopyranosyl pentadecaoligosaccharide backbone with alpha-L-arabinofuranosyl side chains alternately attached at C-2 and C-3 of the middle galactose residue of each consecutive beta-(1-->6)-linked galactotriose unit of the backbone, were synthesized with isopropyl 3-O-allyl-2,4-di-O-benzoyl-1-thio-beta-D-galactopyranoside (6), 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (7), 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl trichloroacetimidate (12), 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (17), 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (19), and 2,6-di-O-acetyl-3,4-di-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (28) as the key synthons. Condensation of 6 with 7 gave the disaccharide donor 8, and subsequent condensation of 8 with 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranosyl-(1-->6)-2-O-acetyl-3,4-di-O-benzoyl-beta-D-galactopyranoside (9) followed by selective deacetylation afforded the tetrasaccharide acceptor 11. Coupling of 11 with 12 gave the pentasaccharide 13, its deallylation followed by coupling with 12, and debenzoylation gave the hexasaccharide 16 with beta-(1-->6)-linked galactopyranose backbone and 2- and 3'-linked alpha-L-arabinofuranose side chains. The octasaccharide 27 was similarly synthesized, while the twentyoside 42 was synthesized with tetrasaccharides 33 or 24 as the donors and 23, 36, 38, and 40 as the acceptors by consecutive couplings followed by deacylation.     

Comparative (1)H NMR and molecular modeling study of hydroxy protons of beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH(2))(7)CH(3) analogues in aqueous solution

The (1)H chemical shifts, coupling constants, temperature coefficients, exchange rates, and inter-residual ROEs have been measured, in aqueous solution, for the hydroxy and amine/amide proton resonances of a set of beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH(2))(7)CH(3) analogues. From the structural data, a few significant structural features could be ascertained, such as a preferential anti-conformation for the amide protons of the N-acetyl and N-propionyl groups. The introduction of systematic modifications at Gal 2-C and Gal 6-C resulted in alterations of the Gal 4-OH, Gal 3-OH, and GlcNAc 3-OH areas, since variations in chemical shifts and temperature coefficient were observed. In order to verify the possibility of hydrogen bonds, molecular dynamics simulations in the gas phase and explicit solvent were performed and correlated with the experimental data. A network of hydrogen bonds to solvent molecules was observed, but no strong intramolecular hydrogen bonding was observed.     

Solution conformation of laminaribioside and (1 → 3)-β-D-glucan from optical rotation

A chiroptical method of conformational analysis is applied to linear (1 → 3)-β-D -glucans and the dimeric analogues β- and α-laminaribioside. The method is based on a recently developed semiempirical calculational model for saccharide optical activity. We conclude that disaccharide conformational energy maps in the literature represent the effective potential energy surface in aqueous solution well. The positive optical rotation observed with long chains in dilute alkaline solution is not characteristic of any single–chain conformation, and must reflect chain association.     

Synthesis of beta-(1-->6)-branched beta-(1-->3) glucohexaose and its analogues containing an alpha-(1-->3) linked bond with antitumor activity

A beta-(1-->6)-branched beta-(1-->3)-glucohexaose, present in many biologically active polysaccharides from traditionally herbal medicines such as Ganoderma lucidum, Schizophyllum commune and Lentinus edodes, was synthesized as its lauryl glycoside 32, and its analogues 18, 20 and 33 containing an alpha-(1-->3) linked bond were synthesized. It is interesting to find that coupling of a 3,6-branched acylated trisaccharide trichloroacetimidate donor 9 with 3,6-branched acceptors 13 and 16 with 3'-OH gave the alpha-(1--> 3)-linked hexasaccharides 17 and 19, respectively, in spite of the presence of C-2 ester capable of neighboring group participation. However, coupling of 9 with 4-methoxyphenyl 4,6-O-benzylidene-beta-D-glucopyranoside (27) selectively gave beta-(1-->3)-linked tetrasaccharide 28. Simple chemical transformation of the tetrasaccharide 28 gave acylated tetrasaccharide trichloroacetimidate 29. Coupling of 29 with lauryl (1-->6)-linked disaccharide 26 with 3-OH gave beta-(1-->3)-linked hexasaccharide 30 as the major product. Bioassay showed that in combination with the chemotherapeutic agent cyclophospamide (CPA), the hexaose 18 at a dose of 0.5-1mg/kg substantially increased the inhibition of S(180) for CPA, but decreased the toxicity caused by CPA. Some of these oligosaccharides also inhibited U(14) noumenal tumor in mice effectively.     

An enzymatically produced novel cyclomaltopentaose cyclized from amylose by an alpha-(1-->6)-linkage, cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->}

A bacterial strain AM7, isolated from soil and identified as Bacillus circulans, produced two kinds of novel cyclic oligosaccharides. The cyclic oligosaccharides were produced from amylose using a culture supernatant of the strain as the enzyme preparation. The major product was a cyclomaltopentaose cyclized by an alpha-(1-->6)-linkage, cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->}. The other minor product was cyclomaltohexaose cyclized by an alpha-(1-->6)-linkage, cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->}. We propose the names isocyclomaltopentaose (ICG5) and isocyclomaltohexaose (ICG6) for these novel cyclic maltooligosaccharides having one alpha-(1-->6)-linkage. ICG5 was digested by alpha-amylase derived from Aspergillus oryzae, cyclomaltodextrin glucanotransferase (CGTase) from Bacillus stearothermophilus, and maltogenic alpha-amylase. On the other hand, ICG6 was digested by CGTase from B. stearothermophilus and B. circulans, and maltogenic alpha-amylase. This is the first report of enzymatically produced cyclomaltopentaose and cyclomaltohexaose, which have an alpha-(1-->6)-linkage in their molecules.     

The structure and conformation of a water-insoluble (1-->3)-,(1-->6)-beta-d-glucan from the fruiting bodies of Pleurotus florida

A water-insoluble glucan, PFPSIN, has been isolated from the aqueous extract of an edible mushroom Pleurotus florida. On the basis of total acid hydrolysis, methylation analysis, periodate oxidation, Smith degradation, and (13)C NMR experiments, the repeating unit of the polysaccharide was established as Conformational analysis revealed the triple helical conformation of this glucan.     

Synthesis of divalent beta-(1-->6)-branched (1-->3)-glucohexaose and trivalent beta-(1-->6)-branched (1-->3)-glucotriose

Hexaose, beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-alpha-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp, based dimers were synthesized by twofold glycosidation of the hexaosyl trichloroacetimidate with hexylene 1,6-diol, diethylene glycol and triethylene glycol, respectively. Meanwhile, a triose, beta-1D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp, based trimer was obtained by glycosidation of the triosyl trichloroacetimidate with a glycerol-derived triol scaffold.     

Identification of bound water molecules in the cyclic tetrasaccharide, cyclo-{-->6}-alpha-d-Glcp-(1-->3)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->)

A structural characterization of bound water molecules in the cyclic tetrasaccharide, cyclo-{-->6}-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->), was carried out by NMR spectroscopy. H-1', 2'-OH, H-3', and 4'-OH of the 3-O-glycosylated residue and H-1 of the 6-O-glycosylated residue were found to cross-relax with protons of bound waters using the double-pulsed field-gradient spin-echo ROESY experiment. In the crystal structure, one water molecule is located in the center of the plate, and its temperature factor is very low, indicating that this water molecule is an intrinsic component.     

NMR characterization of the structure of a beta-(1-->3)-D-glucan isolate from cultured fruit bodies of Sparassis crispa

SCG, a purified beta-d-glucan, obtained from Sparassis crispa, exhibits various biological activities including an antitumor effect, enhancement of the hematopoietic response in cyclophosphamide-induced leukopenic mice, and induction of the production of cytokines. The mechanisms of these effects have been extensively investigated; however, an unambiguous structural characterization of SCG is yet to be achieved. It is well accepted that the biological effects of beta-glucan depend on its primary structures, conformation, and molecular weight. In the present study, we examine the difference of biological effects among beta-glucans, elucidate the primary structure of SCG, and compare with SPG from Schizophyllum commune using NMR spectroscopy. Our data reveal that SCG but not SPG induce cytokine production from bone marrow-derived dendritic cells (BMDCs) and their major structural units are a beta-(1-->3)-d-glucan backbone with single beta-(1-->6)-d-glucosyl side branching units every three residues.     

Syntheses of arabinogalactans consisting of beta-(1-->6)-linked D-galactopyranosyl backbone and alpha-(1-->3)-linked L-arabinofuranosyl side chains

Two arabinogalactosyl nonasaccharides, beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->3)]-beta-D-Galp-(1-->6)-beta-D-Galp-(1-->6)-beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->5)-alpha-L-Araf-(1-->3)]-beta-D-Galp-(1-->6)-beta-D-Galp and beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->5)-alpha-L-Araf-(1-->3)]-beta-D-Galp-(1-->6)-beta-D-Galp-(1-->6)-beta-D-Galp-(1-->6)-[alpha-L-Araf-(1-->3)]-beta-D-Galp-(1-->6)-beta-D-Galp, were synthesized as their 4-methoxyphenyl glycosides with 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (1), 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (14), 4-methoxyphenyl 3-O-allyl-2,4-di-O-benzoyl-beta-D-galactopyranoside (2), 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (5), 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl trichloroacetimidate (8), and 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl-(1-->5)-2,3-di-O-benzoyl-alpha-L-arabinofuranosyl trichloroacetimidate (11), as the key synthons. The tetra- (10) and pentasaccharide donor (13), and the tetra- (20) and pentasaccharide acceptor (22) were synthesized based on these synthons through simple transformations. Coupling of 22 with 10, and coupling of 20 with 13 and subsequent deacylation gave nonasaccharides 24 and 26, respectively, consisting of beta-(1-->6)-linked glactopyranosyl backbone and alpha-(1-->3)-linked arabinofuranosyl side chains of different size.     

Automated docking of alpha-(1-->4)- and alpha-(1-->6)-linked glucosyl trisaccharides and maltopentaose into the soybean beta-amylase active site

The Lamarckian genetic algorithm of AutoDock 3.0 was used to dock alpha-maltotriose, methyl alpha-panoside, methyl alpha-isopanoside, methyl alpha-isomaltotrioside, methyl alpha-(6(1)-alpha-glucopyranosyl)-maltoside, and alpha-maltopentaose into the closed and, except for alpha-maltopentaose, into the open conformation of the soybean beta-amylase active site. In the closed conformation, the hinged flap at the mouth of the active site closes over the substrate. The nonreducing end of alpha-maltotriose docks preferentially to subsites -2 or +1, the latter yielding nonproductive binding. Some ligands dock into less optimal conformations with the nonreducing end at subsite -1. The reducing-end glucosyl residue of nonproductively-bound alpha-maltotriose is close to residue Gln194, which likely contributes to binding to subsite +3. In the open conformation, the substrate hydrogen-bonds with several residues of the open flap. When the flap closes, the substrate productively docks if the nonreducing end is near subsites -2 or -1. Trisaccharides with alpha-(1-->6) bonds do not successfully dock except for methyl alpha-isopanoside, whose first and second glucosyl rings dock exceptionally well into subsites -2 and -1. The alpha-(1-->6) bond between the second and third glucosyl units causes the latter to be improperly positioned into subsite +1; the fact that isopanose is not a substrate of beta-amylase indicates that binding to this subsite is critical for hydrolysis.     

Synthesis of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->3)]-beta-D-GlcpOLauryl, an oligosaccharide with anti-tumor activity

A concise and effective synthesis of lauryl heptasaccharide 17 was achieved from the key intermediates lauryl 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2,4-di-O-benzoyl-beta-D-glucopyranoside (10) and isopropyl 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-1-thio-beta-D-glucopyranoside (15). The key trisaccharide glycosyl acceptor 10 was constructed by coupling 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (3) with lauryl 6-O-acetyl-2,4-di-O-benzoyl-beta-D-glucopyranoside (9), followed by deacetylation. The thioglycoside donor 15 was obtained by condensation of 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11) with isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (12), followed by debenzylidenation and acetylation. A bioassay of the inhibition of S180 noumenal tumors showed that lauryl heptasaccharide 17 could be employed as a potential agent for cancer treatment.     

Studies on the alpha-(1-->4)- and alpha-(1-->8)-fucosylation of sialic acid for the total assembly of the glycan portions of complex HPG-series gangliosides

A synthetic study on alpha-(1-->4) and alpha-(1-->8)-fucosylation of sialic acid is reported, with the ultimate aim being the total assembly of the glycan portion of HPG-series gangliosides. In both types of fucosylations, the combination of a phenylthio fucosyl donor and a 1,5-lactamized acceptor provided high-yielding glycosylations to afford alpha-fucosyl-sialic acid sequences. The obtained alpha-Fucp-(1-->8)-NeupNAc glycan having a 1,5-lactam bridge has been successfully transformed into the corresponding glycosyl donor.