Mimics of the Structural Elements of Type III Group B Streptococcus Capsular Polysaccharide. Part I: Synthesis of a Carboxylate-Containing Pentasaccharide

Abstract

A carboxylate-containing pentasaccharide, methyl O-(β-d-galactopyranosyl)-(1→4)-O-(β-d-glucopyranosyl)-(1→6)-O-{3-O-[(S)-1-carboxyethyl]-β-d-galactopyranosyl-(1→4)-O}-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-β-d-galactopyranoside (27) was synthesized by block condensation of suitably protected donors and acceptors. Phenyl 3-O-benzyl-4,6-di-O-chloroacetyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (17) was condensed with methyl 2,4,6-tri-O-benzyl-β-d-galactopyranoside (4) to afford a disaccharide, methyl O-(3-O-benzyl-4,6-di-O-chloroacetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (18). Removal of chloroacetyl groups gave 4,6-diol, methyl 0-(3-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (19), in which the primary hydroxy group (6-OH) was then selectively chloroacetylated to give methyl O-(3-O-benzyl-6-O-chloroacetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (20). This acceptor was then coupled with 2,4,6-tri-O-acetyl-3-O-[(S)-1-(methoxycarbonyl)ethyl]-α-d-galactopyranosyl trichloroacetimidate (14) to afford a trisaccharide, methyl O-{2,4,6-tri-O-acetyl-3-O-[(S)-l-(methoxycarbonyl)ethyl]-β-d-galactopyranosyl}-(1→4)-O-(3-O-benzyl-6-O-chloroacetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (21). Removal of the 6-O-chloroacetyl group in 21 gave 22, which was coupled with 4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-2,3,6-tri-O-acetyl-α-d-glucopyranosyl trichloroacetimidate (23) to yield protected pentasaccharide 24. Standard procedures were used to remove acetyl groups and the phthalimido group, followed by N-acetylation, and debenzylation to yield pentasaccharide 27 and a hydrazide by-product (28) in a 5:1 ratio, respectively. Compound 27 contains a complete repeating unit of the capsular polysaccharide of type III group B Streptococcus in which terminal sialic acid is replaced by an (S)-1-carboxyethyl group.     

Two new triterpenoids from Nauclea officinalis

Two new triterpenoids and three 27-nor-triterpenoids were isolated from the stems (with bark) of Nauclea officinalis. Their structures were identified to be 2β,3β,19α,23-tetrahydroxy-urs-12-en-28-oic acid (1), 2β,3β,19α,23-tetrahydroxy-urs-12-en-28-O-[β-d-glucopyranosyl (1-2)-β-d-glucopyranosyl] ester (2), pyrocincholic acid 3β-O-α-l-rhamnopyranoside (3), pyrocincholic acid 3β-O-α-l-rhamnopyranosy1-28-O-β-d-glucopyranosyl ester (4), pyrocincholic acid 3β-O-α-l-rhamnopyranosy1-28-O-β-d-glucopyranosyl-(1-6)-β-d-glucopyranosyl ester (5) by spectroscopic methods including 1D, 2D NMR and HR-MS analyses. The cytotoxic activity of 1–5 against lung cancer A-549 cells was also investigated.     

Two new quercetin glycoside derivatives from the fruits of Gardenia jasminoides var. radicans

Two new quercetin glycoside derivatives named quercetin-3-O-[2-O-trans-caffeoyl-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside] (1) and quercetin-3-O-[2-O-trans-caffeoyl-β-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside] (2) along with three known flavonoids, 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (3), 5,7-dihydroxy-8-methoxyflavone (4) and kaempferol 3-O-β-d-glucopyranoside (5), were isolated from the fruits of Gardenia jasminoides var. radicans. The structures of the new compounds were determined by means of extensive spectroscopic analysis (1D, 2D NMR and HR-ESI-MS), glycoside hydrolysis and sugar HPLC analysis after derivatisation. This is the first report on the isolation of a pair of compounds with α or β-l-rhamnopyranosyl configuration from plant and the first detail assignment of their NMR data.     

SYNTHESIS OF 3-O-ARABINOSYLATED (1→6)-β-D-GALACTAN EPITOPES

Two tetrameric arabinogalactans, β-D-galactopyranosyl-(1→6)-β-D-galactopyranosyl-(1→6)-[α-L-arabinofuranosyl-(1→3)]-D-galactopyranose (14) and α-L-arabinofuranosyl-(1→3)-β-D-galactopyranosyl-(1→6)-β-D-galactopyranosyl-(1→6)-D-galactopyranose (25), which are good candidates for CCRC-M7 epitope characterization, were synthesized efficiently using a convergent strategy. Migration of an acceptor acetyl group proved to be an obstacle to synthesis, but regioselective glycosylation or 4-O-benzyl protection of the acceptor circumvented this problem allowing efficient synthesis of the 1→6 linked target compounds.     

A FACILE SYNTHESIS OF MANNOSE TRI- AND TETRASACCHARIDE REPEATING UNITS OF FUNGAL CELL-WALL POLYSACCHARIDE FROM MICROSPORUM AND TRYCHOPHYTON SPECIES

ABSTRACT

A facile synthesis of the trisaccharide α-D-mannopyranosyl-(1→2)-α-D-mannopyranosyl-(1→6)-α-D-mannopyranose and the tetrasaccharide α-D-mannopyranosyl-(1→2)-α-D-mannopyranosyl-(1→6)-α-D-mannopyranosyl-(1→6)-D-mannopyranose, the repeating units of fungal cell-wall polysaccharide from Microsporum gypseum and Trychophyton, was achieved using α-(1→2)-linked disaccharide imidate as the donor. The disaccharide imidate was prepared from the self-condensation of 3,4,6-tri-O-benzoyl-1,2-O-allyloxyethylidene-β-D-mannopyranose.     

SYNTHESIS OF A MANNOTETRAOSE—THE REPEATING UNIT OF THE CELL-WALL MANNANS OF MICROSPORUM GYPSEUM AND RELATED SPECIES OF TRYCHOPHYTON

A tetrasaccharide, α-D-mannopyranosyl-(1→2)-α-D-mannopyranosyl-(1→6)-α-D-mannopyranosyl-(1→6)-D-mannopyranose (1), the repeating unit of the cell-wall mannans of Microsporum gypseum and related species of Trychophyton, was synthesized using 6-O-acetyl-2,3,4-tri-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate (5) and 2-O-acetyl-3,4,6-tri-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate (13) as the glycosyl donors in “the inverse Schmidt” procedure.     

Structural Elucidation of an Elicitor-Active Oligosaccharide,LN-3, Prepared from Algal Laminaran

Abstract

The primary structure of an elicitor-active oligosaccharide, LN-3, prepared from partially hydrolyzed algal laminaran was determined by means of the analyses of glycosyl-linkage, fragments by acetolysis, and glycosyl-sequence. The elicitor-active oligosaccharide, LN-3, is a pyridylaminated hepta-β-d-glucoside which was shown to have the following linear structure: β-d-Glcp(1→6)-β-d-Glcp(1→3)-β-d-Glcp(1→3)-β-d-Glcp(1→3)-β-d-Glcp(1→6)-β-d-Glcp(1→3)-Glc-PA.     

A new caffeoylgluconic acid derivative from the nearly ripe fruits of Evodia rutaecarpa

A new caffeoylgluconic acid derivative, trans-caffeoyl-6-O-d-gluconic acid methyl ester (1), together with two known compounds named trans-caffeoyl-6-O-d-glucono-γ-lactone (2) and trans-caffeoyl-6-O-d-gluconic acid (3), was isolated from the nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth.. These compounds were isolated by various separation methods associated with the UPLC-Q-TOF-MS technique. Their structures were elucidated on the basis of extensive spectroscopic methods.     

A Convenient Synthesis of Pyranosyl-1-carbaldoximes

Abstract

A simple high-yielding procedure is described for the preparation of tri-O-acetyl-β-l-fucopyranosylformaldoxime (1) involving stannate(II)-mediated reduction of the readily accessible tri-O-acetyl-β-l-fucopyranosylnitromethane (3). The d-mannosyl, d-glucosyl, d-galactosyl, and d-xylosyl analogues 7–12 were prepared similarly. The structure of tetra-O-acetyl-β-d-mannopyranosylformaldoxime (7) was determined by X-ray crystallography.     

SYNTHESIS OF THE C-DISACCHARIDE α-C(1→3)-L-FUCOPYRANOSIDE OF N-ACETYLGALACTOSAMINE[1]

Radical C-glycosidation of racemic 5-exo-benzeneselenyl-6-endo-chloro-3-methylidene-7-oxabicyclo[2.2.1]heptan-2-one ((±)-2) with α-acetobromofucose (3) provided a mixture of α-C-fucosides that were reduced with NaBH₄ to give two diastereomeric alcohols that were separated readily. One of them ((?)-6) was converted into (?)-methyl 2-acetamido-4-O-acetyl-2,3-dideoxy-3-C-(3′,4′,5′-tri-O-acetyl-2′,6′-anhydro-1′,7′-dideoxy-α-L-glycero-D-galacto-heptitol-1′-C-yl)-α -D-galactopyranuronate ((?)-11) and then into (?)-methyl 2-acetamido-2,3-dideoxy-3-C-(2′,6′-anhydro-1′,7′-dideoxy-α-L-glycero-D-galacto-heptitol-1′-C-yl)-β -D-galactopyranoside ((?)-1), a new α-C(1→3)-L-fucopyranoside of N-acetylgalactosamine. Its ¹H NMR data shows that this C-disaccharide (α-L-Fucp-(1→3)CH₂-β-D-GalNAc-OMe) adopts a major conformation in solution similar to that expected for the corresponding O-linked disaccharide, i.e., with antiperiplanar σ(C-3′,C-2′) and σ(C-1′,C-3) bonds.     

NON-ANOMERIC SUGAR ISOUREAS

Six non-anomeric isourea derivatives of d-fructose (7, 8), d-glucose (9, 10), 6-deoxy-l-altrose (11) and l-rhamnose (12) were synthesized from the precursors 1–6 by a CuCl-catalyzed addition of a non-glycosidic OH-group to DCC and DIPC, respectively. Subsequently, the isoureido group of phenyl 2,3,4-tri-O-benzyl-6-O-(N,N′-dicyclohexylisoureido)-β-d-glucopyranoside (10) was replaced by an azido and a thioacetyl group, respectively, yielding the corresponding 6-deoxy-6-azido-d-glucopyranoside (13) and 6-deoxy-6-thioacetyl-d-glucopyranoside (14) in moderate to good yields.     

Preparation of Anhydro-Thiohexofuranosides from Methyl Fructofuranosides Via the Thio-Mitsunobu Reaction 1

Abstract

Methyl α-D-fructofuranoside was transformed regioselectively into the corresponding 6-S-thioacetate in one step by use of the thio-Mitsunobu reaction. Reaction of the trimesylate derived from this thioacetate with sodium hydrogen carbonate led to the thietanosugar methyl 4,6-anhydro-1,3-di-O-mesyl-4-thio-α-D-tagatofuranoside. Methyl β-D-fructofuranoside gave the corresponding 6-S-thioacetate and, with excess thioacetic acid, the 1-S,6-S-bis-thioacetate. Whereas this mono-thioacetate did not yield a thietano derivative, the bis-thioacetate gave the bis-thietane methyl 1,3:4,6-dianhydro-1,4-dithio-β-D-sorbofuranoside with sodium hydrogen carbonate.     

Three new triterpenoid saponins from the roots of Ardisia crenata and their cytotoxic activities

Three new triterpenoid saponins, ardisicrenoside O (1), ardisicrenoside P (2) and ardisicrenoside Q (3) together with three known compounds, 3β,16α-dihydroxy-30-methoxy-28, 30-epoxy-olean-12-en, cyclamiretin A 3-O-β-d-glucopyranosyl-(1→2) -α-l-arabinopyranoside and cyclamiretin A 3-O-β-d-glucopyranosyl-(1→4) -α-l-arabinopyranoside were isolated from the roots of Ardisia crenata Sims. Their structures were determined by one- and two-dimensional NMR techniques, including HSQC, HMBC and TOCSY experiments, as well as acid hydrolysis and GC analysis. All isolates were evaluated for the cytotoxic activities on two human cancer cell lines and compounds 3, 5 and 6 showed significant cytotoxicity.     

New flavonol glycosides from the leaves of Caragana brachyantha

Two new flavonol glycosides, brachysides C and D, together with three known flavonol glycosides, were isolated from the leaves of Caragana brachyantha. The structures of brachysides C and D were elucidated on the basis of detailed spectroscopic analysis as quercetin 5-O-[α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside]-7-O-[α-l-rhamnopyranoside] and quercetin 5-O-[α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside]-7-O-[α-l-rhamnopyranoside]-4′-O-[α-l-rhamnopyranoside], respectively. The presence of flavonol tetra- and triglycosides bearing a sugar moiety at position 5 was the first report from this genus Caragana.     

A new acylated flavonoid tetraglycoside with anti-inflammatory activity from Tipuana tipu leaves

A new acylated kaempferol glycoside, kaempferol 3-O-α-l-rhamnopyranosyl-(1 → 6)-O-[β-d-glucopyranosyl-(1 → 2)-4-O-acetyl-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranoside, has been isolated from the leaves of Tipuana tipu (Benth.) Lillo growing in Egypt, along with three known flavonol glycosides, kaempferol 3-O-rutinoside, quercetin 3-O-rutinoside (rutin) and kaempferol 3-O-[α-l-rhamnopyranosyl-(1 → 6)]-[α-l-rhamnopyranosyl-(1 → 2]-β-d-glucopyranoside. Structure elucidation was achieved through different spectroscopic methods. Structure relationship with anti-inflammatory activity using carrageenin-induced rat paw oedema model is discussed.     

Dhasingreoside: new flavonoid from the stems and leaves of Gaultheria fragrantissima

A new flavonoid, dhasingreoside (1) and seven known compounds, quercetin 3-O-β-d-galacturonopyranoside (2), quercetin 3-O-β-d-galactopyranoside (3), quercetin 3-O-β-d-glucuronopyranoside (4), quercetin 3-O-α-l-rhamnopyranoside (5), (–)-epicatechin (6), salicylic acid (7) and gaultherin (8), have been isolated from the shade-dried stems and leaves of Gaultheria fragrantissima, commonly known as ‘Dhasingre’ in Nepal. The structures were elucidated on the basis of physical, chemical and spectroscopic methods. Among known compounds, five compounds (3–6 and 8) were isolated for the first time from G. fragrantissima. In vitro antioxidant activity of all the isolated compounds was evaluated by 1,1-diphenyl-2-picrylhydrazyl free radical-scavenging assay. Dhasingreoside (1) and other compounds (2–6) showed significant free radical-scavenging activity.     

ASCOPYRONE P: CHEMICAL SYNTHESIS FROM d-GLUCOSE

The pyranone, 1,5-anhydro-4-deoxy-d-glycero-hex-1-en-3-ulose (1) (ascopyrone P), has been synthesised in eight steps from d-glucose. The key steps were deacetylation of 3,6-di-O-acetyl-1,5-anhydro-d-glycero-hex-3-en-2-ulose (8) to give isomers and hydrates of 1,5-anhydro-4-deoxy-d-glycero-hex-3-en-2-ulose (9). Isomerisation of this mixture afforded 1,5-anhydro-4-deoxy-d-glycero-hex-1-en-3-ulose (1) (ascopyrone P) in a moderate yield.     

A new triterpenoid glycoside from the leaves and stems of Duranta repens

A new triterpenoid glycoside (1) was isolated from the methanol extract of the leaves and stems of Duranta repens L. (Verbenaceae) along with 14 known compounds consisting of eight triterpenoids, four iridoids, one phenylethanoid glycoside and one flavonoid. The chemical structure of 1 was determined to be bayogenin 3-O-[β-D-glucopyranoside]-28-O-[α-L-rhamnopyranosyl-(1→5)-O-β-D-apiofuranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-O-α-L-arabinopyranosyl] ester, based on spectroscopic data. In addition, the inhibitory effects of the isolates on lipoxygenase activity were examined. Among them, acteoside and apigenin resulted in 94 ± 3.6% and 82 ± 4.7% inhibition, respectively, at 0.5 mM.     

SYNTHESIS AND APPLICATION OF SPACER-MODIFIED L-FUCOSE ANALOGUES[1]

Starting from 6-O-tert-butyldimethylsilyl-2,3;4,5-di-O-isopropylidenealdehydo-D-galactose (1), the carbon backbone elongated GDP-L-fucose analogue 15 bearing a chromophore tag at the end of a spacer was synthesized. Additionally, the analogues of 3-L-fucosyllactose (29) and 2′-L-fucosyllactose (36), where the fucosyl moiety is marked by a five atom alkyl chain at C-5, were prepared as labeled oligosaccharides of human milk.     

Synthesis of 4-Octuloses from a Derivative of d-Fructose

Abstract

Reaction of 2,3:4,5-di-O-isopropylidene-β-d-arabino--hexos-2-ulo-2,6-pyranose (1) with (methoxycarbonylmethylene)triphenylphosphorane in either dichloromethane or methanol gave methyl (E)-2,3-dideoxy-4,5:6,7-di-O-isopropylidene-β-d-arabino-oct-2-ene-4-ulo-4,8-pyranosonate (2) or a 1:2.3 mixture of 2 and its Z-isomer (3), respectively. Bishydroxylation of 2 with osmium tetraoxide gave a mixture of methyl 4,5:6,7-di-O-isopropylidene-β-d-glycero-d-galacto- (4) and -d-glycero-d-ido-oct-4-ulo-4,8-pyranosonate (5) which were carefully resolved by column chromatography. Compound 4 was transformed into its 2,3-di-O-methyl derivative (6) which was deacetonated to 7 and subsequently degraded to dimethyl 2,3-di-O-methyl-(+)-L-tartrate (8). On the other hand, acetonation of a mixture of 4 and 5 gave the corresponding tri-O-isopropylidene derivatives (9) and (10). Compounds 4 and 5 were reduced with LiAlH₄ to the related 4,5:6,7-di-O-isopropylidene-β-d-glycero-d-galacto- (11) and β-d-glycero-d-ido-oct-4-ulo-4,8-pyranose (12). Treatment of 11 and 12 with acetone/PTSA/CuSO₄ only produced the acetonation at the C-2,3 positions. Finally, compounds 11 and 12 were deacetonated to the corresponding D-glycero-d-galacto- (15) and D-glycero-d-ido-oct.-4-ulose (16).