Alkylation of active methylene compounds with alcohols catalyzed by an iridium complex

Base-free catalytic alpha-alkylation of active methylene compounds with primary alcohols was successfully achieved using an [IrCl(cod)](2) complex in the presence of PPh(3) to afford the corresponding saturated alpha-alkylated products in good yields.     

Effect of core-shell micelle formation on the redox properties of phenothiazine-labeled poly(ethyl glycidy ether)-block-poly(ethylene oxide)

Redox properties of phenothiazine-labeled poly(ethyl glycidy ether)-block-poly(ethylene oxide) (PT-EGE_n-b-EO_m) are reversibly changed by core-shell micelle formation. In the temperature range higher than the critical micellization temperature (cmt), the anodic potential of PT group positively shifts and concomitantly its anodic current decrease, or levels off compared to those of the reference polymer PT-EO_m without the thermo-responsive EGE_n segment. The former alteration is caused by incorporation of hydrophobic PT groups into a core of the micelle and the latter by the decrease in the diffusion coefficient of PT groups due to formation of the core-shell micelles. The cmt value and the temperature-dependent alteration in the redox properties strongly depend on the polymer structure, especially the length of thermo-responsive EGE_n segment. The electrochemically determined hydrodynamic radii of the polymer aggregates seem to be overestimated, compared to the values reported for the aggregates of other thermo-responsive polymers with similar molecular weights, implying the presence of electrochemically inactive PT groups in the copolymers having longer thermo-responsive segments.     

Synthesis and antiulcer activity of optical isomers of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid (rebamipide).

The enantiomers of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid [(+/-)-1, rebamipide, OPC-12759], a new antiulcer agent that enhances mucosal resistance, were synthesized from optically active alpha-amino acid derivatives of 2(1H)-quinolinone. The key intermediates, alpha-amino acid derivatives, were prepared by asymmetric synthesis and optical resolution. The (+)-1 was about 1.7 times as potent as the (-)-isomer in antiulcer activity against ethanol-induced gastric ulcers.     

Studies on the synthesis of condensed pyridazine derivatives. IV. Synthesis and anxiolytic activity of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-ones and related compound.

A series of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)- ones and related compounds were synthesized and evaluated for their ability to displace 3H-diazepam from rat brain membranes in vitro, and to prevent bicuculline induced convulsions in mice in vivo. Compounds with a 4'-methoxyphenyl (36) or 4'-chlorophenyl group (37, 39--42) as 2-aryl substituents showed prominent activities in both the in vitro and in vivo tests. Among them, 2-(4'-chlorophenyl)-5,6-dihydro- (37) and 2-(4'-chlorophenyl)-5,6-dihydro-10-fluoro-(1)benzothiepino[5,4-c]+ ++pyridazin- 3(2H)-one 7-oxides (41) showed activity twice as potent as diazepam in an anticonflict test (Vogel type, rats) while exhibiting less muscle relaxation (rotarod test, mice) and augmentation of gamma-aminobutyric acid-induced chloride current (Icl) in isolated frog sensory neurones than diazepam. Compound 37 (Y-23684) was selected from this series as a candidate for further development. The structure-activity relationships are discussed.     

Marginal electron density and density-difference functions

Summary For visual analysis of the density reorganization and distortion, the one-dimensional cut (x, y ₀,z ₀) and the two-dimensional cut (x, y, z ₀) of the three-dimensional electron density difference function (x, y, z) are frequently employed. However, these cut functions do not satisfy any sum rules in contrast to the original difference function (x, y, z). To avoid this difficulty, the use of the marginal electron density functions _x (x) and _xy (x, y) and their difference functions _x (x) and _xy (x, y) is proposed. The marginal densities are condensation of the three-dimensional density onto a particular plane or line of our interest, and they satisfy the sum rule (i.e., the conservation of the number of electrons) exactly. Some basic properties of the marginal electron density are clarified for typical diatomic molecular orbitals. An illustrative application is given for the bonding and antibonding processes in the H₂ system.     

Vanadate-stimulated release of hepatic lipase activity from liver.

Vanadate stimulated the release of rat hepatic lipase activity from liver slices into an incubation medium in a time- and dose-dependent manner. Insulin, however, failed to have this stimulatory action, and the release by heparin was recognized, but was not additive to that by vanadate. Amiloride, an inhibitor of tyrosine kinase in some receptors and of the Na+/H+ exchange system suppressed the vanadate-stimulated release. Biochanin A, a different type of tyrosine kinase inhibitor than amiloride, also suppressed the effect of vanadate. The stimulation by vanadate was clearly preserved in Na(+)-, K(+)-, or Ca(2+)-free medium, suggesting that neither the Na+/H+ exchange system, Na+, K(+)-adenosine triphosphatase, nor Ca(2+)-influx into cells is involved in the action of this substance. These results suggest that vanadate-stimulated release of the enzyme activity is associated with the activation of the tyrosine kinase activity.     

Synthesis and modification of new biodegradable copolymers: Serine/glycolic acid based copolymers

Serine/glycolic acid-based biodegradable polymers have been prepared by ring-opening homopolymerization of 3-(O-benzyl)-L -serinylmorpholine-2,5-dione, and ring-opening copolymerization of the morpholine-2,5-dione derivative and L -lactide/ϵ-caprolactone. The homopolymerization was carried out in the melt at 165°C for 3 min using stannous octanoate as the initiator and continued at lower reaction temperatures (130–150°C) for 48 h, using a molar ratio of monomer and initiator of 1000 yielded a polymer of M_n = 4000. The polymer prepared by homopolymerization of the morpholine-2,5-dione derivative was composed of alternating protected serine and glycolic acid residues. Random copolymers of serine and glycolic acid and L -lactic acid/ϵ-caprolactone were synthesized by copolymerization reaction of 3-(O-benzyl)-L -serinylmorpholine-2,5-dione and lactide or ϵ-caprolactone in the melt at 165°C for 3 min and further reaction at 130°C using stannous octanoate as an initiator. The polymers were deprotected and functionalized through the side chain hydroxyl group of serine residues with an acrylate moiety for applications in injectable drug delivery, cell encapsulation. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 1901–1907, 1997     

Synthetic studies on psiguadial B: Construction of bicyclo[4.3.1]decane skeleton via double cyclization reaction of alkyne dicobalt complex

A new method for constructing the polycyclic skeleton of psiguadial B (1), a meroterpenoid isolated from an evergreen shrub of Myrtaceae, was developed. The terpenoid substructure of 1 was constructed on the basis of a cascade double cyclization reaction of an alkyne dicobalt complex, which afforded the bicyclo[4.3.1]decane derivative having a benzyl group with the correct configuration. The substituted aromatic ring was introduced to the bridgehead position of the intermediate, and bromination under radical conditions followed by intramolecular cyclization reaction resulted in formation of the benzopyran moiety in a stereoselective manner.     

Electrical conductance of solutions of lithium nitrate in 1,3-diaminopropane

Electrical conductances and densities of the LiNO₃-1,3-diaminopropane system have been measured as a function of composition and temperature. The results suggest that the solvent molecules may act as bridges between Li⁺ ions at higher concentration of LiNO₃.     

Applications of an automated apparatus for two-dimensional electrophoresis, Model TEP-1, for microsequence analyses of proteins.

Two-dimensional electrophoresis has become a rapid and powerful separation method for the preparation of samples for sequence analysis depending on the development of automated microsequencers accompanied by a blotting technique. We have constructed an automated apparatus for two-dimensional electrophoresis, Model TEP-1, which allows precise analytical runs under computer-control with a fully automated transfer from the first- to the second-dimensional gel. In the present paper we describe several applications of TEP-1 followed by blotting and sequencing to reveal the primary structure of proteins in a complex mixture. Several known and unknown proteins were analyzed. Enzymatic digests of proteins could be directly applied onto the TEP-1, in which a gel of lower molecular weight proteins was used as the second dimension. Subsequent blotting and sequencing provided internal sequence information. The use of TEP-1, followed by blotting, provides spots containing ca. 10-100 pmol protein. These figures permitted the identification of 10-40 amino acid residues from the N-terminus. The TEP-1 provides a simple and rapid separation of complex mixtures obtained from natural sources and chemical, biological or genetic products.