Study of the Conformational Variety of the Oligosaccharide Substrates of Neuraminidases from Pathogens using Molecular Modeling

Analysis of the conformational variety of the oligosaccharide fragments of the human glycan receptors LSTa (α-D-Neu5Ac-(2-3)-β-D-Gal-(1-3)-β-D-GlcNAc-(1-3)-β-D-Gal(1-4)-D-Glc) and LSTc (α-D-Neu5Ac-(2-6)-β-D-Gal-(1-3)-β-D-GlcNAc-(1-3)-β-D-Gal(1-4)-D-Glc) in aqueous solution has been performed with the comprehensive use of molecular modeling and statistical data processing followed by determination of major and minor stabilized conformers and selection of relevant topologies. The sialic acid ring conformational free energy landscape for both pentasaccharides has been reconstructed and analyzed giving a specification of the most probable distorted ring conformations of the basic chair ¹C₄ structure. The obtained results are in a good agreement with experimental data generated by nuclear magnetic resonance spectroscopy and X-ray crystallography.     

Cucumarioside G4 — A new triterpenglycoside from the holothurian Eupentacta fraudatrix

A minor glycoside — cucumarioside G₄ (I) — has been isolated from the total triterpeneglycosides of the holothurianEupentacta fraudatrix, and its structure has been determined by physical and chemical methods as 16β-acetoxyholosta-7,23E-diene-3β, 25-diol 3-O-(3-O-methyl-β-D-xylopyranosyl)-(1→3)-O-β-D-glucopyranosyl-(1→4)-O-β-D-quinovopyransoyl-(1→2)-(4-O-(sodium sulfato)-β-D-xylopyranoside)].     

Photochemistry of dienones-VIII: The low temperature photochemistry of (z)-β-ionone and its photo-isomers

The isomerizations of (E)-β-ionone 1, and of mixtures of the isomeric pyran 2 and (Z)-β-ionone 3 in CD₃OD as solvent on direct irradiation with λ 254 nm and on triplet photo-sensitization have been studied at temperatures ? - 50°, where the thermal isomerization between 2 and 3 is fully inhibited. The direct irradiation of 1 at -60° leads to 3 and (Z)-retro-γ-ionone 4 as primary products; 3 is subsequently rapidly photo-converted into mainly 2. Evidence is presented that 4 is also a primary photoproduct from both 2 and 3. The quantum yield ratio φ_2→4:φ_3→4 ?0.50. On starting with either 1 or mixtures of 2 and 3 the same photo-stationary equilibrium ratio of 1-3 is eventually obtained, viz 1:2:3 ?17:72:11. 4 is photostable relative to 1–3.The perdeuterobenzophenone triplet photo-sensitization with λ 366 nm at -50° of 1 leads to 3 as the sole primary product, which isomer on triplet sensitization yeilds both 1 and 2. The triplet sensitized conversion is much faster for (Z)- than (E)-β-ionone. On starting with either 1 or mixtures of 2 and 3, eventually the same photo-stationary state is obtained, viz 1:2:3?39:46:15. (Z)-retro-λ-ionone 4 is not formed in the triplet sensitized irradiations of 1,2 and 3 and in the direct irradiation it apparently results from the singlet excited state of the three substrates.The UV spectrum of the (unstable) (Z)-β-ionone 3 has been indirectly determined; its absorption occurs at lower wavelength and is of lower intensity than that of the (E)-isomer 1.     

Glycosides of marine invertebrates. XV. A new triterpene glycoside — Holothurin A1 — From Caribbean holothurians of the family Holothuriidae

A glycoside, holothurin A₁ has been isolated from the polar glyosidic fractions of the holothuriansH. floridana andH. grisea. The complete structure of the glycoside has been established; it is: 3β-[0-(3-0-methyl-β-D-glucopyranosyl)-(1 → 3)-0-β-D-glucopyranosyl-(1 → 4)-0-β-D-quinovopyranosyl-(1 → 2)-(4-sulfato-β-D-xylopyranosyl)oxy]holosta-9(11)-ene-12α,17α,22ξ-triol. Details of the IR and¹H and¹³C NMR spectra of the compounds obtained are given.     

Antigenotoxic ketosteroid from the red algae Jania adhaerens

A new ketosteroid, 6β,16β-dihydroxycholest-4-en-3-one (1), in addition to the known 6β-hydroxycholest-4-en-3-one (2), 6β-hydroxycholest-4,22-dien-3-one (3) and 16β-hydroxy-5α-cholestan-3,6-dione (4), was isolated from the red alga Jania adhaerens. The structures were assigned on the basis of (1)H- and (13)C-NMR experiments. The new compound (1) was evaluated for its genotoxic and cytotoxic activities and found to possess protective antigenotoxicity in human peripheral blood cells.     

Triterpene glycosides of Hedera taurica

From the leaves of Crimean ivy we have isolated the previously known glycosides 3-O-α-L-Ara_p-28-O-[O-α-L-Rha_p-(1→4)-O-β-D-Glc_p-(1→6)-β-D-Glc_p]hederagenin, 3-O-[O-α-L-Rha_p-(1→2)-α-L-Ara_p]-28-O-[O-α-L-Rha_p-(1→4)-O-β-D-Glc_p-(1→6)-β-D-Glc_p]oleanic acid and -hederagenin, and 3-O-[O-α-L-Rha_p-(1→2)-α-L-Ara_p]-28-O-[O-β-D-Glc_p-(1→6)-β-D-Glc_p]hederagenin and a new one: tauroside H₁ — 3-O-[O-α-L-Rha_p-(1→2)-O-α-L-Ara_p]-28-O-[O-α-L-Rha_p-(1→4)-O-β-D-Glc_p-(1→6)-β-D-Glc_p]echinocystic acid.     

Major terpenoids from Telekia speciosa flowers and their cytotoxic activity in vitro

In addition to known constituents of Telekia speciosa, an acetone extract from ray florets of the plant yielded: 5,5?-dibutoxy-2,2?-bifuran (1), 5,5?-diisobutoxy-2,2?-bifuran (2), α-tocopherol (3), β-tocopherol (4), loliolide palmitate (5), a mixture of calenduladiol esters - 16β-hydroxylupeol-3-O-palmitate (7) and 16β-hydroxylupeol-3-O-myristate (8), 1-epiinuviscolide (12), inuviscolide (13), 3-epiisotelekin (16), 4α-hydroxy-9β,10β-epoxy-1β(H)-11(13)-guaien-8α,12-olide (17), 4α-hydroxy-1β(H)-9(10),11(13)-guaiadien-8α,12-olide (18), loliolide (19) and 4β,10β-dihydroxy-1α(H),5α(H)-11(13)-guaien-8α,12-olide (20). Calenduladiol esters and asperilin (14) were the major constituents of the extract. Their cytotoxic effect on human normal prostate epithelial cells (PNT-2), human prostate carcinoma cell lines, human skin fibroblasts (HSF) and human melanoma cell lines was examined in vitro. Triterpene esters showed no cytotoxicity against nearly all cell lines tested, except for Du145 prostate carcinoma cells (IC₅₀ – 62.0 μΜ). Asperilin displayed activity against the cell lines under study, especially against three tested lines of melanomas (A375, IC₅₀ – 17.6 μΜ, WM793, IC₅₀ – 28.2 μΜ and Hs 294T, IC₅₀ – 29.5 μΜ).     

Synthesis of disaccharides for the study of human blood antibodies capable of recognizing the inner Glcβ1-3GalNAc disaccharide fragment of bacterial polysaccharides

Disaccharides with the terminal Glcβ1-3 motif were synthesized as probes for studying human blood antibodies. An antibody isolated using Glcβ1-3GalNAcα–Sepharose was found to bind the inner part of the polysaccharide [–4GlcA6LThr3Acβ1-6Galβ1-6Glcβ1-3GalNAc6Acβ1–]_n as evidenced by the use of a printed glycan array and inhibition assays.     

On the Specificity of Anti-Sulfoglucuronosyl Glycolipid Antibodies 1

Abstract

The mouse monoclonal anti-human HNK-1 antibody (also variously known as L2, Leu-7, CD57, VC1.1), monoclonal anti-sulfoglucuronosyl glycosphingolipids (SGGLs) antibody (mAb NGR50), and human sera from patients with demyelinating neuropathy and IgM paraproteinemia, are known to react with not only SGGLs, including sulfoglucuronosyl paragloboside (SGPG) and sulfoglucuronosyl lactosaminyl paragloboside (SGLPG), but also glycoproteins, such as myelin-associated glycoprotein (MAG), PO, PMP22, and certain adhesion molecules. These antigens are known to possess the so-called HNK-1 epitope (3-sulfoglucuronic acid, SGA) moiety. To further define the precise structural requirement of this carbohydrate epitope, we chemically synthesized 14 SGGLs, and their nonsulfated derivatives with defined carbohydrate chain lengths and aglycone structures. The various aglycones include ceramide, 2-(tetradecyl)hexadecyl (B30), and 2-(trimethylsilyl)ethyl (SE). These synthetic SGGLs were tested for their immunoreactivity with the above antibodies by high-performance thin-layer chromatography (HPTLC)-immunoblotting and ELISA. The anti-HNK-1 antibody (VC1.1) reacted with SGGL analogues containing a minimum of two sugars (SGA-Gal-Cer), but not with non-sulfated derivatives of SGGLs nor with SGGLs having a modified ceramide structure. mAb NGR50, on the other hand, reacted with only SGPG and SGLPG. A human patient serum (LT) reacted with all synthetic SGGLs except those with an SE aglycone structure. On the other hand, another human patient serum (YT). like the anti-HNK-1 antibody, VC1.1, reacted with SGPG, SGLPG, and SGGL analogues containing a minimum of two sugars (SGA-Gal-Cer). All antibodies reacted more strongly with synthetic SGGLs with longer carbohydrate chains. These results indicate that anti-SGGL antibodies recognize a minimum of two sugars bearing the following structure (3-sulfoglucuronosyl β 1-3 galactosyl, SGA-Gal-) and that the aglycone (“ceramide”) structure appears to play an important role for antibody-antigen interaction.

     

Steroid glycosides from the starfish Crossaster papposus

Two new steroid glycosides have been isolated from an ethanolic extract of the starfishCrossaster papposus — crossasterosides P₁ and P₂. On the basis of chemical transformations and spectral characteristics, the structure of crossasteroside P₁ has been established as (24R)-24-ethyl-5α-cholestane-3β,6β,8,15α,16β,29-hexaol 29-O-[2-O-methyl-β-D-xylopyranosyl-(1 → 2)-β-D-galactofuranoside]. Crossasteroside P₂ is its 4β-hydroxy analogue.     

Trifluoromethyl- and difluoromethyl-β-lactams as useful building blocks for the synthesis of fluorinated amino acids, dipeptides, and fluoro-taxoids

Enantiopure 1-acyl-3-hydroxyl-4-CF₂H-azetidin-2-ones and 1-acyl-3-hydroxy-4-CF₃-azetidin-2-ones serve as versatile intermediates for the syntheses of CF₂- and CF₃-containing α-hydroxy-β-amino acids, dipeptides, and taxoid anticancer agents. Both enantiomers of 3-hydroxy-4-CF₂H-β-lactams can be obtained in high yields through the diethylaminosulfur trifluoride (DAST) reaction of the corresponding enantiopure 4-formyl-β-lactam that is prepared through [2+2] cycloaddition of acetoxyketene to a 3-methyl-2-butenaldimine, followed by enzymatic optical resolution and ozonolysis. (+)-3-Hydroxy-4-CF₃-β-lactams and (−)-3-hydroxy-4-CF₃-β-lactams can also be readily obtained in enantiopure form through [2+2] cycloaddition of a CF₃-imine with a ketene, followed by enzymatic optical resolution. Practical processes for the preparations of these enantiopure 3-hydroxy-4-R_f-β-lactams as well as their synthetic applications are described.     

The Studies of Fast Atom Bombardment Mass Spectrometry of Melezitose Derivatives

Melezitose is a kind of nonreducing sugar, its structure is 3-(α-D-glucopyranosyl)-β-D-fructofuranosyl-α-D-glucopyranose, it is a principal constituent of Alhagi pseudalhagi Desv.manna, which is used as a drug in Uygur medicine.     

Culcitosides C2 and C3 from the starfishCulcita novaeguineae

Two steroid glycosides not previously described have been isolated from the digestive system of the starfishCulcite novaeguiniae, and these have been called culcitosides C₂ and C₃. With the aid of chemical and spectral methods, the chemical structure of C₂ has been established as 24ξ-methyl-5α-cholestane-3β,4β,6α,8,15β,16β,28-heptaol 28-O-[O-(2,4-di-O-methyl-β-D-xylopyranosyl)-(1 → 2)-α-L-arabinofuranoside, and that of C₃ as its 4-deoxy analogue.     

Synthese von tri- und tetrasaccharid-einheiten des O-antigens aus Aeromonas salmonicida

The following oligosaccharide sequences containing the repeating unit of the O-specific chain of lipopolysaccharides from aeromonas salmonicida have been synthesized: α-D-Glcp-(1→3)-α-L-Rhap-(1 →3)-β-D-ManpNAcO(CH₂)₈CO₂Me, α-D-Glcp-(1 →4)-α-D-Glcp-(1→3)-α-L-Rhap-(1→3)-β-D-ManpNAcO(CH₂)₈CO₂Me and α-D-Glcp(1→4)-α-D-Glcp-(1→3)-[β-D-ManpNAc(1→4)]-L-Rha.     

The synthesis of 3-deazapyrimidine nucleosides related to uridine and cytidine and their derivatives

Condensation of 2,4-bis(trimethylsilyloxy)pyridine ( 1 ) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide ( 2 ) gave 4-hydroxy-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 3 ). Deblocking of 3 gave 4-hydroxy-1-β-D-ribofuranosyl-2-pyridone (3′-deazauridine) ( 4 ). Treatment of 4 with acetone and acid gave 2′,3′-O-isopropylidene-3-deazauridine ( 6 ). Reaction of 4 with diphenylcarbonate gave 2-hydroxy-1-β-D-arabinofuranosyl-4-pyridone-O₂←2′-cyclonucleoside ( 7 ) which established the point of gylcosidation and configuration of 4 . Base-catalyzed hydrolysis of 7 gave 4-hydroxy-1-β-D-arabinofuranosyl-2-pyridone (3-deazauracil arabinoside) ( 12 ). Fusion of 1 with 3,5-di-O-p-toluyl-2-deoxy-D-erythro-pentofuranosyl chloride ( 5 ) gave the blocked anomeric deoxynucleosides 8 and 10 which were saponified to give 4-hydroxy-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazauridine) ( 11 ) and its α anomer ( 9 ). Condensation of 4-acetamido-2-methoxypridine ( 13 ) with 2 gave 4-acetamido-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 14 ) which was treated with alcoholic ammonia to yield 4-acetamido-1-β-D-ribofuranosyl-2-pyridone ( 15 ) or with methanolic sodium methoxide to yield 4-amino-1-β-D-ribofuranosyl-2-pyridone (3-deazacytidine) ( 16 ). Condensation of 13 and 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride ( 17 ) gave the blocked nucleoside 22 which was treated with base and then hydrogenolyzed to give 4-amino-1-β-D-arabinofuranosyl-2-pyridone (3-deazacytosine arabinoside) ( 23 ). Fusion of 13 with 5 gave the blocked anomeric deoxynucleosides 18 and 20 which were deblocked with methanolic sodium methoxide to yield 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazacytidine) ( 21 ) and its a anomer 19 . The 2′-deoxy-erythro-pentofuranosides of both 3-deazauracil and 3-deazacytosine failed to obey Hudson's isorotation rule but did follow the “quartet”-“triplet” anomeric proton splitting pattern in the ¹H nmr spectra.     

Synthese von 3-Oxacholestanen

Successive treatment of 5α-cholestan-3-one ( 1 ) with O₂ under basic conditions and then NaBH₄ led to 5α-3-oxa-cholestan-2-one ( 5 ). Analogous reactions with 5β-cholestan-3-one ( 6 ) yielded 5α-4-oxa-cholestan-3-one ( 7 ) and 5 ξ-3-oxa-cholestan-4-one ( 8 ). 4-Cholesten-2-one ( 10 ), which was prepared starting from 4-cholesten-3-one, was isomerized by methanolic KOH to give a mixture of 5α-cholest-3-en-2-one ( 11 ) and 5β-cholest-3-en-2-one ( 12 ). 5β-Cholestane-2,3-dione ( 17 ) was synthesized from 4β-bromo-5β-cholestan-3-one ( 13 ). Ozonolysis of the dione 17 and subsequent NaBH₄ reduction of the oxidation product gave both 5β-2-oxa-cholestan-3-one ( 18 ) and 5β-3-oxa-cholestan-2-one ( 19 ).     

Stapelogenin,vermutliche Struktur. Glykoside und Aglykone, 276. Mitteilung

Stapelogenin, C₂₁H₃₀O₄, shows a double bond and two hydroxyl groups which can be acetylated. On the grounds of UV.-, IR.-, and NMR-spectra as well as mass spectra, the probable structure is that of a 3β, 12β-dihydroxy-(18, 20β), (14β, 20α)-diepoxy-Δ⁵-pregnene ( 1 ). The exact position of the hydroxyl group, assumed to be 12β, is particularly unsure, as it could also be situated 11α- or 12α-position.     

An in vitro study on probable inhibition of cerebrovascular disease by salidroside as a potent small molecule against induction of protein amyloid fibrils and cytotoxicity

Protein aggregation and associated amyloid formation is linked with several harmful human pathophysiologies including Alzheimer's, Parkinson's, and cerebrovascular diseases. A potential approach for modulating and exploring amyloid fibrillization is the control of protein self-assembly. Herein, anti-aggregation effects of salidroside, its influence on the kinetics of amyloid fibrillization of Aβ_1-42 peptide and its cytotoxicity against cerebrovascular endothelial cells (bEnd.3) were assessed by using a wide range of spectroscopic and cellular techniques. The present outcome of Thioflavin T (ThT) and 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence, Congo red (CR), and circular dichroism (CD) analyses indicated that salidroside potentially inhibits protein fibril formation. The cellular studies inferred that salidroside protects bEnd.3 cells against Aβ_1-42 oligomers -triggered cytotoxicity through modulation of oxidative stress [reactive oxygen species (ROS), superoxide dismutase (SOD) and catalase (CAT) activities] and apoptosis (caspase-3 activity). Therefore, the data signifies the role of salidroside as a promising small molecule in inhibiting Aβ_1-42 aggregation and associated cerebrovascular endothelial cell toxicity. Hence, salidroside can serve as a potential inhibitor in the therapeutic advancement to combat cerebrovascular diseases.     

Structures of cucumariosides C1 and C2 — Two new triterpene glycosides from the holothurian Eupentacta fraudatrix

Two new triterpene glycosides — cucmariosides C₁ and C₂ — have been isolated from the Far Eastern holothurianEupentacta (=Cucumaria)fraudatrix Djakonov et Baranova. Their structures have been established with the aid of¹³C NMR and PMR spectroscopy, partial acid hydrolysis, periodate oxidation, and methylation as 16β-acetoxy-3-{[3-O-methyl-β-D-xylopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)] [β-D-xylopyranosyl-(1→2)]-β-D-quinovopyranosyl-(1→2)-β-D-xylopyranosyloxy}holosta-7,23,24(cis)-triene and 16β-acetoxy-3-{[3-O-methyl-β-D-xylopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)] [β-D-xylopyranosyl-(1→2)]-β-D-quinovopyranosyl-(1→2)-β-D-xylopyranosyloxy}holosta-7,22,24(trans)-triene, respectively.     

Synthesis of haloconduritols from an endo-cycloadduct of furan and vinylene carbonate

A method for preparing haloconduritols having a conduritol-A construction is described. A mixture of endo- and exo-cycloadduct derivatives prepared from the Diels-Alder reaction of furan and vinylene carbonate was converted into diacetate derivatives by hydrolysis (K₂CO₃/MeOH) followed by acetylation (Ac₂O/pyridine). Boron trihalide (BBr₃ or BCl₃)-assisted ring-opening of the endo-diacetate in CH₂Cl₂ at −78°C gave (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol 1,2-diacetate from which the corresponding triacetate was prepared by acetylation (AcCl). trans-Esterification of the triacetate (MeOH/HCl) afforded (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol (X=Br or Cl). BF₃-Assisted ring-opening of the endo-diacetate in CH₂Cl₂ gave (1α,2α,3β,6β)-6-chloro-4-cyclohexene-1,2,3-triol 1,2-diacetate by means of halogen exchange.