Direct Catalytic Asymmetric Mannich‐Type Reaction of Thioamides

Taking the reins : The title transformation of thioamides and N‐diphenylphosphinoyl imines is described. By harnessing the power of cooperative catalysis between a soft Lewis acid and a hard Brønsted base, thioamide carbon pronucleophiles can furnish Mannich products (see scheme). Divergent transformation of the thioamide functionality highlights the utility of this methodology.

     

Enantioselective synthesis of endohedral metallofullerenes

Endohedral metallofullerenes are promising materials in biomedical and material sciences. In particular, they are of interest as agents for magnetic resonance imaging (MRI), photovoltaic devices, and semimetallic components. The synthesis of chiral endofullerenes represents one step further in the potential use of these carbon allotropes; however, this step has not been addressed so far. In this regard, enantiopure endofullerenes are expected to open new avenues in fields in which chirality is a key issue. Here, the synthesis and characterization of the first chiral endohedral metallofullerenes, namely, chiral bis-adducts of La@C(72), are reported. Eight optically active isomers were obtained by enantioselective 1,3-dipolar cycloaddition of a N-metalated azomethine ylide onto a non-isolated-pentagon rule metallofullerene derivative, La@C(72)(C(6)H(3)Cl(2)), catalyzed by a copper chiral complex. The chiral bis-adducts of La@C(72), isolated by nonchiral HPLC, showed optical purities as high as 98% as revealed by the remarkable positive or negative Cotton effects observed in the circular dichroic spectra.     

Copper-mediated intermolecular direct biaryl coupling

Copper-mediated intermolecular direct biaryl coupling of arylazines and azoles via dual C-H bond cleavage proceeds even without palladium catalysts. The reaction system shows the high potential of copper salts in direct C-H arylation chemistry and provides a new approach to biaryl motifs, which are ubiquitous in pharmaceuticals and functional materials.     

Antitumor effect of liposomal histone deacetylase inhibitor-lipid conjugates in vitro

Histone deacetylase inhibitor (HDACI), suberoylanilide hydroxamic acid (SAHA), approved by the Food and Drug Administration (FDA) for the treatment of cutaneous T cell lymphoma, is a promising new treatment strategy for various cancers. In this study, we hypothesized that a liposomal formulation of HDACI might efficiently deliver HDACI into tumors. To incorporate HDACI efficiently into the liposomal membrane, we synthesized six HDACI-lipid conjugates, in which polyethylene glycol(2000) (PEG(2000))-lipid or cholesterol (Chol) was linked with a potent hydroxamic acid, HDACI, SAHA or K-182, by cleavable linkers, such as ester, carbamide and disulfide bonds. Liposomal HDACI-lipid conjugates were prepared with distearoylphosphatidylcholine (DSPC) and HDACI-Chol conjugate or with DSPC, Chol and HDACI-PEG-lipid conjugates, and their cytotoxicities were evaluated for human cervix tumor HeLa and mouse colon tumor Colon 26 cells. Among the liposomes, liposomal oleyl-PEG(2000)-SAHA conjugated with SAHA and oleyl-PEG(2000) via a carbamate linker showed higher cytotoxicity via hyperacetylation of histone H3 and induction of caspase 3/7 activity. These results suggested that liposomal HDACI-lipid conjugates may be a potential tool for cancer therapy.     

Stereo‐ and Regioselective Direct Multi‐Deuterium‐Labeling Methods for Sugars

Deuterium‐labeled sugars can be utilized as powerful tools for the architectural analyses of high‐sugar‐containing molecules represented by the nucleic acids and glycoproteins, and chiral building blocks for the syntheses of new drug candidates (heavy drugs) due to their potential characteristics, such as simplifying the ¹H NMR spectra and the stability of C? D bonds compared with C? H bonds. We have established a direct and efficient synthetic method of deuterated sugars from non‐labeled sugars by using the heterogeneous Ru/C‐catalyzed H–D exchange reaction in D₂O under a hydrogen atmosphere with perfect chemo‐ and stereoselectivities. The direct H–D exchange reaction can selectively proceed on carbons adjacent to the free hydroxyl groups, and the deuterium labeling of various pyranosides (such as glucose and disaccharides), as well as furanosides, represented by ribose and deoxyribose was realized. Furthermore, the desired number of deuterium atoms can be freely incorporated into selected positions by the site‐selective protection of the hydroxyl groups using acetal‐type protective groups because the deuterium exchange reaction never proceeds on positions adjacent to the protected hydroxyl groups.     

以聚乳酸为侧链的光学活性聚苯乙炔的合成与表征

通过4-溴苯甲醇和三甲基硅基乙炔的Sonagashira偶联反应与三甲基硅基的脱除反应,合成4-乙炔基苯甲醇.以4-乙炔基苯甲醇为引发剂,以有机氮杂环化合物DBU为催化剂,常温常压下进行丙交酯的活性开环聚合反应,采用1H-NMR和GPC对产物结构、分子量与分子量分布进行表征分析,结果表明,合成以了苯乙炔为端基的聚乳酸大...     

Experimental Validation of Intermediate Termination in RAFT Polymerization with Dithiobenzoate via Comparison of Miniemulsion and Bulk Polymerization Rates

To understand if either of two controversial models for the retardation by RAFT agents is applicable, styrene polymerization using dithiobenzoate as the RAFT agent is carried out in both bulk and miniemulsion systems with the same rates of radical generation and the same RAFT agent concentrations. Miniemulsion polymerization with average diameters of the miniemulsion droplets of ≈107 nm is by far faster than in bulk, and the obtained rate of polymerization agrees well with the calculated results assuming a bimolecular termination between propagating radical and intermediate radical, generated by the addition reaction of propagating radical to the RAFT agent, which shows that the intermediate termination is the major reason for rate retardation by the RAFT agent.

     

Size-Controlled Synthesis of Nano-Zeolites and Their Application to Light Olefin Synthesis

For the application of zeolites as heterogeneous catalysts, low diffusion resistance for hydrocarbons within the micropore is essential for improving product selectivity and catalyst lifetime. This problem has been overcome by reducing the crystal size. This review introduces size-controlled preparation of nano-sized zeolites via hydrothermal synthesis in water/surfactant/organic solvent (emulsion method) and their application to heterogeneous catalysts. The ionicity of the hydrophilic group in surfactant molecules and the concentration of the Si source affected the crystallinity and morphology of zeolites prepared using the emulsion method. When using a non-ionic surfactant, mono-dispersed silicalite-1 nanocrystals ~60?nm in diameter were successfully prepared. Nano- and macro-ZSM-5 zeolites with crystal sizes of ~150?C200?nm and 1.5???m, respectively, were prepared and applied to n-hexane cracking and acetone-to-olefin reactions to investigate the effect of zeolite crystal size on catalytic stability and light olefin yield. Application of nano-zeolite to light olefin production was effective in achieving faster mass transfer of hydrocarbon molecules within the micropore, which led to improvements in olefin yields and catalyst lifetime.     

LSI-based amperometric sensor for bio-imaging and multi-point biosensing

We have developed an LSI-based amperometric sensor called "Bio-LSI" with 400 measurement points as a platform for electrochemical bio-imaging and multi-point biosensing. The system is comprised of a 10.4 mm × 10.4 mm CMOS sensor chip with 20 × 20 unit cells, an external circuit box, a control unit for data acquisition, and a DC power box. Each unit cell of the chip contains an operational amplifier with a switched-capacitor type I-V converter for in-pixel signal amplification. We successfully realized a wide dynamic range from ±1 pA to ±100 nA with a well-organized circuit design and operating software. In particular, in-pixel signal amplification and an original program to control the signal read-out contribute to the lower detection limit and wide detection range of Bio-LSI. The spacial resolution is 250 μm and the temporal resolution is 18-125 ms/400 points, which depends on the desired current detection range. The coefficient of variance of the current for 400 points is within 5%. We also demonstrated the real-time imaging of a biological molecule using Bio-LSI. The LSI coated with an Os-HRP film was successfully applied to the monitoring of the changes of hydrogen peroxide concentration in a flow. The Os-HRP-coated LSI was spotted with glucose oxidase and used for bioelectrochemical imaging of the glucose oxidase (GOx)-catalyzed oxidation of glucose. Bio-LSI is a promising platform for a wide range of analytical fields, including diagnostics, environmental measurements and basic biochemistry.