A novel strategy for designing irreversible inhibitors of metalloproteases: acetals as latent electrophiles that interact with catalytic nucleophile at the active site

A new strategy for design of irreversible inactivators for carboxypeptidase A (CPA), a prototypic zinc protease, has been developed by exploiting the property of acetals to generate an oxacarbenium ion intermediate in the conversion into the corresponding carbonyl compounds. The design strategy is exemplified by 2-benzyl-5-alkyl-3,5-dioxapentanoic acids (1a-c). Interestingly, (R)-1b is slightly more potent than an (S)-1b as an inactivator of CPA.     

Enzymatic resolution of 2-substituted tetrahydroquinolines. Convenient approaches to tricyclic quinoxalinediones as potent NMDA-glycine antagonists

Two approaches leading to the enantiomerically pure tricyclic quinoxalinedione class of NMDA-glycine antagonists using enzymatic resolutions are described. An intermediate, racemic methyl 1,2,3,4-tetrahydroquinoline-2-carboxylate 3, was resolved to (S)-3 in 97% ee and 47% yield (E=67) using -chymotrypsin. In an improved method, hydrolysis of another intermediate, racemic methyl 1,2,3,4-tetrahydroquinoline-2-acetate 4, with Novozym^® 435 provided the desired (S)-4 in high enantioselectivity and yield (93% ee, 50%, E=94).     

Novel multi-chalcogen ring systems with three different chalcogen atoms: synthesis,structure and redox property of five-membered trichalcogenaheterocycles

The molecular structure of novel five-membered trichalcogenaheterocycles with three different chalcogen atoms, sulfur, selenium and tellurium, has been determined by crystallographic studies.     

Mizoroki-Heck arylation of alpha,beta-unsaturated acids with a hybrid fluorous ether, F-626: facile filtrative separation of products and efficient recycling of a reaction medium containing a catalyst

The Mizoroki-Heck reaction was carried out using a fluorous ether F-626 as the solvent and a fluorous Pd carbene complex as the catalyst. When carboxylic acids are the products, separation of both the F-626 and the Pd catalyst from the products can be conveniently carried out by simple filtration. The F-626 filtrates containing the Pd catalyst can be recycled.     

5-azahexenoyl radicals cyclize via nucleophilic addition to the acyl carbon rather than 5-exo homolytic addition at the imine

Molecular orbital calculations predict that the 5-azahexenoyl radical ring closes via nucleophilic addition to the acyl carbon to afford the 5-exo product; CCSD(T)/cc-pVDZ/ /BHLYP/cc-pVDZ calculations predict energy barriers of 36.1 and 46.9 kJ mol-1 for the exo and endo cyclization modes of the 5-azahexenoyl radical, respectively.     

Formation mechanism of an “onionlike” multilayered structure by reconstruction of the morphology of micron-sized,monodisperse poly(methyl methacrylate)/polystyrene composite particles with the solvent-absorbing/solvent-releasing method

The formation mechanism of the onionlike multilayered morphology of micron-sized, monodisperse poly(methyl methacrylate) (PMMA)/polystyrene (PS) (1/1 w/w) composite particles by the solvent-absorbing/solvent-releasing method was discussed. It was concluded that the orientation of PMMA components at the outer interface of toluene-swollen particles with water is the trigger and that PMMA-g-PS operates to stabilize inner multilayer interfaces for the formation of the onionlike multilayered morphology.Part CCLV of the series Studies on suspension and emulsion     

Facile synthesis of α-functionalized vinyl sulfides bearing β-trifluoromethyl group: a highly potential CF3-containing building blocks

The β-(trifluoromethyl)vinylsulfides on treatment with n-BuLi/TMEDA were readily lithiated at α-position of the sulfanyl group, and the generated α-lithiovinylsulfides were trapped with a variety of electrophiles to give the corresponding β-trifluoromethyl-α-functionalized vinylsulfides in good to high yields.     

ATP-induced focal adhesion kinase activity is negatively modulated by phospholipase D2 in PC12 cells

Extracellular ATP has been known to modulate various cellular responses including mitogenesis, secretion and morphogenic activity in neuronal cells. In the ATP-induced morphogenic activity, focal adhesion kinase(s) such as Fak have been suggested to play a critical role. Binding of ATP to its specific cell surface receptor in PC12 cells induces phospholipase D (PLD) activity. However, the role of PLD on ATP-induced Fak activation in PC12 cells remains unclear. In this study, we investigated the role of PLD on the ATP-induced Fak activation and paxillin phosphorylation using two established cell lines: wild type PLD2- and lipase-inactive mutant PLD2-inducible PC12 cells. Stimulation of cells with ATP caused PLD2 activation via classical protein kinase C activation. ATP also induced Fak activation, and paxillin phosphorylation, and were dramatically reduced by wild type PLD2 overexpression but not by lipase-inactive mutant PLD2 overexpression. When the PC12 cells were pretreated with propranolol, a specific inhibitor for phosphatidic acid phosphohydrolase resulting in the accumulation of PA, ATP-induced Fak activation and paxillin phosphorylation were also reduced. We found that inhibition of tyrosine phosphatases by pervanadate completely blocked PLD2-dependent Fak and paxillin dephosphorylation. Taken together, we suggest that PLD2 activity might play a negative role in ATP-induced Fak and paxillin phosphorylation possibly through tyrosine phosphatases.     

Effect of phthalates on the stability and performance of AgBF4-PVP membranes for olefin/paraffin separation

The presence of a phthalate in dry polymer membranes consisting of polyvinylpyrrolidone (PVP) and AgBF4, AgBF4-PVP, provides long-term stability and better performance for the separation of propylene/propane gas mixtures.     

Carbohydrate-coated nanocapsules from amphiphilic rod-coil molecule: binding to bacterial type 1 pili

Stable carbohydrate-coated nanocapsules designed as multivalent nanoscaffolds for selective interactions with receptors are able to encapsulate guest molecules within their interior and to bind efficiently to FimH adhesin of bacterial type 1 pili.