Synthetic Studies on Sialoglycoconjugates 91: Total Synthesis of Gangliosides GD1C and GT1A

Abstract

A first total synthesis of gangliosides GD1c and GT1a containing Neu5Acα(2→8) Neu5Acα(2→3)Gal residue in their non-reducing terminal is described. Condensation of methyl O-[methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylono-1¹,9-lactone) -4,7- di-O-acetyl-3,5-dideoxy-D-glycero-α-D-galcto-2-nonulopyranosyranosylanate]-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-D-gala-ctopyranoside (1) with 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-galactopyranosyl)- (1→4) -O -(2,3,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (2) or 2-(trimethylsilyl)ethyl O-(2-acetamido-6-O-benzyl-2-deoxy-β-D-galactopyranosyl)-(1→4)-(9-[methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)]-O-(2,6-di-O-benzyl-β-D-galactopyranosyl) - (1→4) - 2,3,6-tri-O-benzyl-β-D-glucopyranoside (3) in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) gave the corresponding hexa-and heptasaccharide derivatives 4 and 5, respectively. These oligosaccharides were converted into the α-trichloroacetimidates 10 and 11 via reductive removal of the benzyl groups and/or benzylidene group, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and treatment with trichloroacetonitrile, which, on coupling with 2-azidosphingosine derivatives 12 or 13, gave the β-glycosides 14 and 15, respectively. Finally, 14 and 15 were transformed, via selective reduction of the azido group, coupling with octadecanoic acid and removal of all protecting groups, into the title gangliosides GD1c 18 and GT1a 19.     

Pulsed laser deposition synthesis of superconducting (Cu,C)Ba2CuOx thin films

(Cu, C)–Ba–O thin films have been deposited at low growth temperature of 450–570 °C by pulsed laser deposition method. A control of CO₂ gas pressure and the growth temperature, usage of BaCu_yO_x pellet target resulted in an expansion of twice c-axis length of BaCuO₂ structure (2c phase) and a significant rise of conductivity. Measurements of in-situ XPS suggest that the 2c phase should be (Cu, C)Ba₂CuO_x [(Cu, C)-1201]. The maximum temperature of onset of the superconducting transition and zero resistance state obtained so far were 60 and 47 K, respectively.     

In situ characterization of transport properties of superconducting (Cu, C)-system thin films

Transport properties of (Cu, C)Ba₂CuO_x [(Cu, C)-1201] thin films have been characterized by in situ temperature dependence of resistivity, without breaking vacuum from the deposition to the measurement. In in situ transport properties measurements, the obtained results reveal that (Cu, C)Ba₂CuO_x films exhibit T_c > 20 K on the cased of conductivity at 290 K (σ_[290 K]) > 4 × 10² S/cm and temperature coefficient of resistivity (TCR) > 1.5 × 10^?3 K^?1, and doping level of them should be in between under-doped and optimally-doped states. Their results suggest that there would be possible to further increases of T_c, and XPS data suggest that (Cu, C)-system should have the excellent dopability in their charge reservoir and the possibility of low anisotropy.     

Extended applications of di-tert-butylsilylene-directed alpha-predominant galactosylation compatible with C2-participating groups toward the assembly of various glycosides

The high versatility of di-tert-butylsilylene(DTBS)-directed alpha-predominant galactosylation have been extended to the construction of difficult glycan sequences. First, to investigate the compatibility of the alpha-predominant reaction with various glycosylation systems a variety of 4,6-O-DTBS-tethered galactosaminyl or galactosyl donors were synthesized efficiently, which have C2-participating groups with a wide variety of leaving groups such as alkylsulfenyl, halide, trichloroacetimidate groups. The results of the detailed examination of the glycosylation reaction using the glycosyl donors showed the wide scope of the 4,6-DTBS-directed alpha-galactosylation. In the next step, the stereoselective construction of alpha-GalN-Ser/Thr sequences was examined by employing the DTBS-directed glycosylation. As a result, various types of serine and threonine derivatives were glycosylated alpha-selectively, producing alpha-GalN-Ser/Thr sequences in high yields. Moreover, the DTBS-directed galactosylation was successfully applied for the synthesis of alpha-tetrasaccharyl-Ser segment of glycophorin A.     

A major urinary protein of the domestic cat regulates the production of felinine, a putative pheromone precursor

Domestic cats spray urine with species-specific odor for territorial marking. Felinine (2-amino-7-hydroxy-5,5-dimethyl-4-thiaheptanoic acid), a putative pheromone precursor, is excreted in cat urine. Here, we report that cauxin, a carboxylesterase excreted as a major urinary component, regulates felinine production. In vitro enzyme assays indicated that cauxin hydrolyzed the felinine precursor 3-methylbutanol-cysteinylglycine to felinine and glycine. Cauxin and felinine were excreted age dependently after 3 months of age. The age-dependent increases in cauxin and felinine excretion were significantly correlated. In mature cats, cauxin and felinine levels were sex-dependently correlated and were higher in males than in females. In headspace gas of cat urine, 3-mercapto-3-methyl-1-butanol, 3-mercapto-3-methylbutyl formate, 3-methyl-3-methylthio-1-butanol, and 3-methyl-3-(2-methyldisulfanyl)-1-butanol were identified as candidates for felinine derivatives. These findings demonstrate that cauxin-dependent felinine production is a cat-specific metabolic pathway, and they provide information for the biosynthetic mechanisms of species-specific molecules in mammals.     

Temperature programmed desorption of F-doped SnO<Subscript>2</Subscript> films deposited by inverted pyrosol technique

Fluorine-doped tin dioxide (FTO) films were deposited on silicon wafers by inverted pyrosol technique using solutions with different doping concentration (F/Sn=0.00, 0.12, 0.75 and 2.50). The physical and electrical properties of the deposited films were analyzed by SEM, XRF, resistivity measurement by four-point-probe method and Hall coefficient measurement by van der Pauw method. The electrical properties showed that the FTO film deposited using the solution with F/Sn=0.75 gave a lowest resistivity of 3.2·10^–4 ohm cm. The FTO films were analyzed by temperature programmed desorption (TPD). Evolved gases from the heated specimens were detected using a quadruple mass analyzer for mass fragments m/z, 1(H⁺), 2(H₂ ⁺), 12(C⁺), 14(N⁺), 15(CH₃ ⁺), 16(O⁺), 17(OH⁺ or NH₃ ⁺), 18(H₂O⁺ or NH₄ ⁺), 19(F⁺), 20(HF⁺), 28(CO⁺ or N₂ ⁺), 32(O₂ ⁺), 37(NH₄F⁺), 44(CO₂ ⁺), 120(Sn⁺), 136(SnO⁺) and 152(SnO₂ ⁺). The majority of evolved gases from all FTO films were water vapor, carbon monoxide and carbon dioxide. Fluorine (m/z 19) was detected only in doped films and its intensity was very strong for highly-doped films at temperature above 400°C.     

A cyclic glucosyl ceramide acceptor as a versatile building block for complex ganglioside synthesis

A cyclic glucosyl ceramide (GlcCer) acceptor has been developed as a versatile building block for the synthesis of complex ganglioside. A macrocyclic GlcCer acceptor, which was the product of intramolecular glycosylation between glucose and ceramide, exhibited high reactivity during the coupling reactions with a variety of complex oligosaccharyl donors, thereby furnishing the corresponding ganglioside frameworks in high yields.     

Light scattering and electrophoretic studies of mixed micelles of ionic and nonionic surfactants

Summary Light scattering and electrophoretic studies have been made of the mixed micelles formed in the systems ofn-dodecyl nonaoxyethylene ether/sodium dodecyl sulfate (NaC₁₂S), andi-octylphenyl nonaoxyethylene ether/NaC₁₂S as a function of the mole ratio of nonionic/ionic surfactants. In the former system the micellar molecular weight increases simply with increasing nonionic content, while in the latter system it rises abruptly when the nonionic content exceeds about 50% by mole. This behaviour would be interpreted by a difference in hydrocarbon-chain attraction between these two systems. The degree of ionic dissociation, , of NaC₁₂S in the mixed micelles increases as the content of the nonionic surfactant increases. This tendency is in accordance with the previous result obtained by pNa and vapor pressure depression data. The value of is closely related to the charge density, , on the surface of the micelle; increasing with decreasing . The micellar charge for NaC₁₂S alone, estimated from electrophoretic data, is much larger than that calculated from light scattering data by using the equation derived byMysels. For this discrepancy, a plausible explanation would be made by the different surfaces of the micelle measured by these two techniques.With 1 figure and 2 tables