Cascade reaction including a formal [5 + 2] cycloaddition by use of alkyne-Co2(CO)6 complex

A new cascade reaction including formal [5?+?2] cycloaddition was developed. Treatment of homocinnamyl alcohol and Co₂(CO)₆-complexed arylpropynal with BF₃·OEt₂ resulted in the generation of hydrobenzocycloheptafuran having an alkyne-Co₂(CO)₆ complex. The reaction consists of 5-membered ring selective Prins cyclization and subsequent Friedel-Crafts cyclization. The cascade reaction was applied to a further multi-step cascade cyclization, which resulted in the formation of more complex polycyclic hydrofurans.     

Stable Sugar‐Chain‐Immobilized Fluorescent Nanoparticles for Probing Lectin and Cells

Sugar chains are important molecules in cellular recognition and signaling, and quantum dots (QDs) are a very powerful tool for in vitro and in vivo imaging. Herein, we report the preparation of stable sugar‐chain‐immobilized fluorescent nanoparticles (SFNPs) and their application to the analysis of sugar‐chain–protein interactions and cellular imaging. SFNPs were easily prepared by mixing CdTe/CdS core/shell QDs with our previously developed sugar‐chain–ligand conjugates. The obtained SFNPs were very stable and could be stored for several months. In the binding analysis, β‐galactose‐ and α‐glucose‐immobilized SFNPs were specifically interacted with Ricinus communis agglutinin I and concanavalin A, respectively, and made into aggregates. The binding interaction was detected visually, fluorescently, or both. In the experiment for cellular imaging, it was found that SFNPs were predominantly taken up by human hepatocyto carcinoma cells (HepG2), suggesting the possible usage of our designed SFNPs for various biochemical analyses of sugar chains.     

Benzyl radical addition reaction through the homolytic cleavage of a benzylic C-H bond

Direct generation of a benzyl radical by C-H bond activation of toluenes and the addition reaction of the resulting radical to an electron deficient olefin were developed. The reaction of dimethyl fumarate with toluene in the presence of Et(3)B as a radical initiator at reflux afforded 2-benzylsuccinic acid dimethyl ester in good yield.     

Molecular manipulation of two- and three-dimensional silica nanostructures by alkoxysilylation of a layered silicate octosilicate and subsequent hydrolysis of alkoxy groups

A novel methodology for constructing molecularly ordered silica nanostructures with two-dimensional (2-D) and three-dimensional (3-D) networks has been developed by using a stepwise process involving silylation of a layered silicate octosilicate with alkoxytrichlorosilanes [ROSiCl(3), R = alkyl] and subsequent reaction within the interlayer spaces. Alkoxytrichlorosilanes react almost completely with octosilicate, bridging two closest Si-OH (or -O(-)) sites on the silicate layers, to form new five-membered rings. The unreacted functional groups, Si-Cl and Si-OR, are readily hydrolyzed by the posttreatment with a water/dimethyl sulfoxide (DMSO) or water/acetone mixture, leading to the formation of two types of silicate structures. The treatment with a water/DMSO mixture produced a unique crystalline 2-D silicate framework with geminal silanol groups, whereas a water/acetone mixture induced hydrolysis and subsequent condensation between adjacent layers to form a new 3-D silicate framework. The 2-D structure is retained by the presence of DMSO molecules within the swelled interlayer spaces and is transformed to a 3-D silicate upon desorption of DMSO. The structural modeling suggests that both of the 3-D silicates contain new cagelike frameworks where solvent molecules are trapped even at high temperature (up to 380 degrees C, in the case of acetone). Both 2-D and 3-D silica structures are quite different from known layered silicates and zeolite-like materials, indicating the potential of the present approach for precise design of various silicate structures at the molecular level.     

Synthesis of polyamides from active N,N′-diacylbis [1,2-benzisothiazol-3(2h)-one]s and 4,4′-oxydianiline under mild conditions

The aminolysis of 3-benzoyloxy-1,2-benzisothiazole and N-benzoyl[1,2-benzisothiazol-3(2H)-one] derived from 1,2-benzisothiazol-3-ol was studied in model systems and was found to give good yields of N-substituted benzamides at room temperature. Solution polycondensation of new bisamides, N,N′-isophthaloyldi[1,2-benzisothiazol-3(2H)-one], and N,N′-adipoyldi[1,2-benzisothiazol-3(2H)-one], proceeded slowly to give polyamides with moderate molecular weights. The chloroform–triethylamine · hydrochloride system was the best polycondensation medium compared with some polar aprotic solvents for the formation of higher-molecular-weight polyamides.     

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as a factor Xa inhibitor II. Substituent effect on biological activities

Intravascular clot formation is an important event in a number of cardiovascular diseases. The prevention of blood coagulation has become a major target for new therapeutic agents. Factor Xa (FXa) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade and represents an attractive target for anticoagulant drug development. We have investigated substituents in the central part of a lead compound (3: M55113), and discovered that compound M55551 (34: (R)-4-[(6-Chloro-2-naphthalenyl)sulfonyl]-6-oxo-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]-2-piperazinecarboxylic acid) is a potent inhibitor of FXa (IC(50)=0.006 microM), with high selectivity for FXa over trypsin and thrombin. The activity of this compound is ten times more powerful than the lead compound.     

Conductance Study of 1 : 1 19-Crown-6 Complexes with Various Mono- and Bivalent Metal Ions in Water

Formation constants (ML) of 1 : 1 19-crown-6 (19C6) complexes with mono- (M+) and bivalent metal ions (M2+) were determined in water at 25 °C by conductometry. The KML value of 19C6 for M+ and M2+ decreases in the order Rb+ K+ > Tl+ > Na+ = Ag+ > Li+ Cs+ and Pb2+ > Ba2+ > Sr2+ > Cd2+ > Ca2+, respectively. The selectivity for the neighboring alkali metal ions in the periodic table is lower for 19C6 than for 18-crown-6 (18C6) except for the case of Rb+ and Cs+. The same is true for the alkaline earth metal ions. Generally, the KML values of 19C6 with M2+ are greater than those with M+. For Na+ and the ions which are smaller in size than Na+ (Li+, Ca2+, Cd2+), the KML value is larger for 19C6 than for 18C6, but the contrary holds for all the other ions of larger sizes than Na+. The limiting ionic molar conductivity (°) of the 19C6–K+ complex in water at 25 °C was determined to be 43. Although 19C6 is larger than 18C6, the 19C6–K+ complex is much more mobile in water than the 18C6–K+ complex.     

Acid-catalyzed transannular cyclization of 3aH-cyclopentene[8]annulene-1,4-(5H,9aH)-diones and some proposed mechanisms

Bicyclic 3aH-cyclopentene[8]annulene-1,4-(5H,9aH)-diones underwent three types of acid-induced transannular reactions, Michael cyclization, [3 + 2] cycloaddition, and Friedel-Crafts ipso-alkylation, depending on the cyclopentenone ring substituent (Me or Ph) and the position of [8]annulenone substituent as well as the nature of acids (BF3, MeSO3H, CF3SO3H). The Me-substituent permitted the Michael reaction for all acids used to give tricyclic diones by the activation of cyclopentenone carbonyl group. However, the Ph-substituent inhibited the Michael reaction for BF3 and MeSO3H but allowed the [3 + 2] cycloaddition and Friedel-Crafts reaction for CF3SO3H depending on the position of annulenone substituent. These CF3SO3H reactions exhibited the following novel rearrangements, affording 2-naphthalenone and 7-acenaphthylene derivatives, respectively. The factors that control the reaction mode of these transannular cyclizations were discussed in view of the constraint twist-boat conformation of [8]annulenone ring as well as the ring substituent effects on the intramolecular cyclization. In addition, these [8]annulenone rings were found to easily undergo the intramolecular [2 + 2] photocyclization to provide the tetracyclic cage compounds which exhibited the facile cycloreversion under the influence of acid.     

A Cell‐Targeted Non‐Cytotoxic Fluorescent Nanogel Thermometer Created with an Imidazolium‐Containing Cationic Radical Initiator

A cationic fluorescent nanogel thermometer based on thermo‐responsive N‐isopropylacrylamide and environment‐sensitive benzothiadiazole was developed with a new azo compound bearing imidazolium rings as the first cationic radical initiator. This cationic fluorescent nanogel thermometer showed an excellent ability to enter live mammalian cells in a short incubation period (10 min), a high sensitivity to temperature variations in live cells (temperature resolution of 0.02–0.84 °C in the range 20–40 °C), and remarkable non‐cytotoxicity, which permitted ordinary cell proliferation and even differentiation of primary cultured cells.