Asymmetric phase-transfer catalysis utilizing chiral quaternary ammonium salts: asymmetric alkylation of glycine imines

O-Alkyl N-anthracenylmethyl derivatives of Cinchona alkaloids can function as enantioselective phase-transfer catalysts. By employing these catalysts in the asymmetric alkylation of glycine imines, one can generate a range of alpha-amino acid derivatives with high levels of enantiomeric excess. It is also possible to generate the catalysts in situ from commercially available chiral amines, which offers the opportunity to evaluate libraries of related structures. This latter approach has been successfully applied to a series of biphenyl quaternary ammonium salts resulting in the development of a new highly selective catalyst and opening up the potential of further expanding the range of alpha-amino acid derivatives that can be prepared.     

Preparation of trehalose and sorbitol fatty acid polyesters by interesterification

Trehalose octaoleate and sorbitol hexaoleate were prepared by a one-stage solvent-free interesterification of methyl oleate with trehalose octaacetate (TOAC) and sorbitol hexaacetate (SOHA), respectively, in the presence of 1–2.5% sodium metal as catalyst. The greatest yield of trehalose octaoleate, 97.5%, and sorbitol hexaoleate, 96.0%, were obtained at a mole ratio of methyl oleate: SOHA of 6:1 and methyl oleate:TOAC of 8:1 at a synthesis time of 2.5 hr, and temperatures of 105–115°C. The structure of both trehalose octaoleate and sorbitol hexaoleate was confirmed by infrared (IR) and nuclear magnetic resonance (C-13 NMR) spectroscopy. Physical properties such as viscosity, HLB, solubility, color, refractive index, specific gravity and density approximated the physical properties of sucrose polyesters (SPE) and vegetable oils. Trehalose octaoleate and sorbitol hexaoleate, as well as sucrose octaoleate, were not susceptible toin vitro lipolysis, suggesting potential application as low calorie oils. Presented at American Oil Chemists’ Society Annual Meeting in New Orleans, LA, in May, 1987.     

Microstructure and Mechanical Properties of Mullite–Silicon Carbide Composites

Mullite-SiC-whisker composites were prepared by powder processing using two commercial SiC whiskers. These composites were prepared by sintering rather than hot-pressing. A mulliteSlC-powder composite and a base line mallite material were also prepared for comparison with the two whisker composite materials. Fracture toughness measurements showed significant enhancement in only one of the whisker composite materials. The microstructure of the four materials was examined by scanning electron microscopy and transmission electron microscopy to assist in the explanation of the mechanical behavior of these composites. The examinations suggested that most of the toughening results from second-phase particles, with only limited toughening from effects associated with whiskers per se. In one case, higher toughness was partially associated with the formation of sialon phase by reaction with the whiskers and the furnace environment.     

Sugar fatty acid ester surfactants: Structure and ultimate aerobic biodegradability

Ultimate aerobic biodegradabilities of an array of sugar ester surfactants were determined by International Standards Organisation method 7827, “Water Quality—Evaluation in an Aqueous Medium of the Aerobic Biodegradability of Organic Compounds, Method by Dissolved Organic Carbon” (1984). The surfactants were nonionic sugar esters with different-sized sugar head groups (formed from glucose, sucrose, or raffinose) and different lengths and numbers of alkyl chains [formed from lauric (C₁₂) or palmitic (C₁₆) acid]. Analogous anionic sugar ester surfactants, formed by attaching an α-sulfonyl group adjacent to the ester bond, and sugar esters with α-alkyl substituents were also studied. It was found that variations in sugar head group size or in alkyl chain length and number do not significantly affect biodegradability. In contrast, the biodegradation rate of sugar esters with α-sulfonyl or α-alkyl groups, although sufficient for them to be classified as readily biodegradable, was dramatically reduced compared to that of the unsubstituted sugar esters. An understanding of the relationship between structure and biodegradability provided by the results of this study will aid the targeted design of readily biodegradable sugar ester surfactants for use in consumer products.     

Δ6 Desaturase mRNA Abundance in HepG2 Cells Is Suppressed by Unsaturated Fatty Acids

The effect of unsaturated fatty acids on the abundance of Δ6 desaturase (D6D) mRNA and the fatty acid composition of HepG2 cell membranes was examined. Supplementation of HepG2 cells with oleic acid (18:1n-9, OA), linoleic acid (18:2n-6, LA), α-linolenic acid (18:3n-3, ALA), arachidonic acid (20:4n-6, AA) or eicosapentaenoic acid (20:5n-3, EPA) reduced D6D mRNA abundance by 39 ± 6.6, 40 ± 2.2, 31 ± 5.2, 55 ± 4.8, and 52 ± 5.0%, respectively, compared with control cells. Despite the reduction in D6D mRNA abundance, the level of D6D conversion products (20:3n-9, EPA and AA) in OA, ALA and LA supplemented cells, respectively, was elevated above that in control cells. Our results suggest that although unsaturated fatty acids decrease the abundance of D6D mRNA by as much as 50%, the conversion of polyunsaturated fatty acids and accumulation of long chain polyunsaturated fatty acids (LCPUFA) in HepG2 cell phospholipids continues to occur.     

Synthesis of aromatase inhibitors and dual aromatase steroid sulfatase inhibitors by linking an arylsulfamate motif to 4-(4H-1,2,4-triazol-4-ylamino)benzonitrile: SAR, crystal structures, in vitro and in vivo activities

4-(((4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)phenyl sulfamate (6 a) was the first dual aromatase-sulfatase inhibitor (DASI) reported. Several series of its derivatives with various linker systems between the steroid sulfatase (STS) and the aromatase inhibitory pharmacophores were synthesised and evaluated in JEG-3 cells. The X-ray crystal structures of the aromatase inhibitors, DASI precursors 42 d and 60, and DASI 43 h were determined. Nearly all derivatives show improved in vitro aromatase inhibition over 6 a but decreased STS inhibition. The best aromatase inhibitor is 42 e (IC(50)=0.26 nM) and the best DASI is 43 e (IC(50 aromatase)=0.45 nM, IC(50 STS)=1200 nM). SAR for aromatase inhibition shows that compounds containing an alkylene- and thioether-based linker system are more potent than those that are ether-, sulfone-, or sulfonamide-based, and that the length of the linker has a limited effect on aromatase inhibition beyond two methylene units. Compounds 43 d-f were studied in vivo (10 mg kg(-1), single, p.o.). The most potent DASI is 43 e, which inhibited PMSG-induced plasma estradiol levels by 92 % and liver STS activity by 98 % 3 h after dosing. These results further strengthen the concept of designing and developing DASIs for potential treatment of hormone-related cancers.     

Synthesis and application of fluorescein- and biotin-labeled molecular probes for the chemokine receptor CXCR4

The design, synthesis, and bioevaluation of fluorescence- and biotin-labeled CXCR4 antagonists are described. The modification of D-Lys8 at an epsilon-amino group in the peptide antagonist Ac-TZ14011 derived from polyphemusin II had no significant influence on the potent binding of the peptide to the CXCR4 receptor. The application of the labeled peptides in flow cytometry and confocal microscopy studies demonstrated the selectivity of their binding to the CXCR4 receptor, but not to CXCR7, which was recently reported to be another receptor for stromal cell-derived factor 1 (SDF-1)/CXCL12.     

Non-steroidal aromatase inhibitors based on a biphenyl scaffold: synthesis, in vitro SAR, and molecular modelling

The synthesis and in vitro biological evaluation (JEG-3 cells) of a series of novel and potent aromatase inhibitors, prepared by microwave-enhanced Suzuki cross-coupling methodology, are reported. These compounds possess a biphenyl template incorporated with the haem-ligating triazolylmethyl moiety, either on its own or in combination with other substituent(s) at various positions on the phenyl rings. The most potent aromatase inhibitor reported herein has an IC(50) value of 0.12 nM, although seven of its congeners are also highly potent (IC(50)相似文献   

Evaluation of Rule-of-Mixtures Predictions of Thermal Expansion in Powder-Processed Ni–Al2O3 Composites

Ni-Al₂O₃ composites containing 5 to 80 vol% Ni were produced using powder processing methods and their thermal expansion behavior was studied using dilatometry. By varying composition and relative particle sizes, either interpenetrating-phase or particle-reinforced microstructures were obtained. Experimentally determined values of the mean thermal expansion coefficient were compared with predictions made using two different rule-of-mixtures (ROM) formulations. Experimental results for interpenetrating-phase composites were in reasonable agreement with linear ROM estimates. Certain particle-reinforced microstructures that contain processing-induced damage did not correlate as well with ROM predictions. By accounting for this damage in ROM models, better agreement with experimental observations was obtained. However, linear ROM predictions were reasonable over the entire composition range.     

The effects of filler size on the properties of thermoplastic polyolefin blends

The effects of filler size on the properties of a thermoplastic polyolefin (TPO) blend were examined by using wollastonite and talc with particle sizes ranging from 1.2 to 40 μm. While addition of filler produced significant changes in the mechanical properties of the blend, filler size affected only impact strength. However, filler size, filler coating, and injection speed had a major effect on the surface properties of the blend. Faster injection produced denser “shear zone layers” which exhibited better scratch resistance and poorer paint adhesion than those obtained with slower injection. Scartch resistance and paint adhesion also decreased with increasing filler particle size. Filler coatings altered the scratch and adhesion properties of the polypropylene (PP) blends.