Synthesis and biological evaluation of a beauveriolide analogue library

Synthesis of beauveriolide III (1b), which is an inhibitor of lipid droplet accumulation in macrophages, was achieved by solid-phase assembly of linear depsipeptide using a 2-chlorotrityl linker followed by solution-phase cyclization. On the basis of this strategy, a combinatorial library of beauveriolide analogues was carried out by radio frequency-encoded combinatorial chemistry. After automated purification using preparative reversed-phase HPLC, the library was tested for inhibitory activity of CE synthesis in macrophages to determine structure-activity relationships of beauveriolides. Among them, we found that diphenyl derivative 7{9,1} is 10 times more potent than 1b.     

Preparation of ultrafiltration membranes of HCEC and CTA blend, and studies of resistance to microbiological degradation and other properties

Blends of high cyanoethylated cellulose (HCEC) (D_s = 2.5) and cellulose triacetate (CTA) (D_s = 2.8) were prepared for evaluation as ultrafiltration membranes. The rejection R_a and water permeability (P_w) of these membranes with respect to bovine serum albumin (BSA), were measured with the variations in composition and conditions of preparation. It was possible to define the reaction conditions and compositions that offered optimum performance with respect to R_a and J_w, and resistance to microbial degradation as well as acid and alkali hydrolysis. The morphology of membrane thereby obtained was characterized by scanning electron microscopy (SEM). The UF membrane cast from a solution of 1,4-dioxane: 12.5 g, acetone: 12.5 g, HCEC: 1.5 g, CTA: 3 g and PEG (MW = 1000): 10.5 g showed the optimum performance of P_w = 10 × 10⁻¹⁰ m³/(m² s Pa), BSA Rejection (R_a) = 99%, (J_w = 17.3 m³/(m² day) at ΔP = 0.2 MPa) and a molecular weight cut off at 4.9 × 10⁴ Da. After immersion in mud for 170 days, reduction of R_a was only 8% for UF membrane containing 10 wt% HCEC blend, and was not observed to be obviously different from the membrane containing more than 30 wt% HCEC blend. The higher permeability and rejection of blend membrane may be attributable to the network structure formed via CTA and HCEC penetration.     

Reactions of 2-amino-, 2-alkylamino-, and 2-piperidino-1-azaazulenes with aryl and chlorosulfonyl isocyanates

Reaction of 2-amino-1-azaazulene with phenyl isocyanate gave 3-phenyl-2H-3,4-dihydro-1,3,4a-triazabenz[5,4-a]azulene-2,4-dione. Reactions of 2-alkylamino-1-azaazulenes with aryl isocyanates gave 2-(N-ethyl-N′-arylureido)-1-azaazulenes initially, which rearranged to N-aryl-2-alkylamino-1-azaazulene-3-carboxamides and successive reaction with another molar amount of aryl isocyanate furnished uracil-fuzed 1-azaazulenes. Reaction of 2-piperidino-1-azaazulene with aryl isocyanate gave N-aryl-2-piperidino-1-azaazulene-3-carboxamide. Reaction of 2-(substituted amino)-1-azaazulenes with chlorosulfonyl isocyanate gave 3-cyano- and 3-chloro-2-(substituted amino)-1-azaazulenes.     

Constituents of seed of Malva verticillata. VII. Structural features and reticuloendothelial system-potentiating activity of MVS-I, the major neutral polysaccharide.

The structural features of MVS-I, the major neutral polysaccharide isolated from the seeds of Malva verticillata L., were elucidated by controlled Smith degradation, methylation analysis, partial acid hydrolysis and enzymic degradation studies. It has a backbone chain composed of beta-1,3-linked D-glucose and D-galactose residues having branches composed of alpha-1,5-linked L-arabinosyl beta-1,4-linked D-galactose and of beta-1,4-linked D-galactosyl beta-1,3-linked D-glucose residues at position 6 of a part of D-galactose units as side chains. MVS-I showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test.     

A novel neutral polysaccharide having activity on the reticuloendothelial system from the root of Glycyrrhiza uralensis

A neutral polysaccharide, named glycyrrhizan UC, was isolated from the root of Glycyrrhiza uralensis Fischer. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was estimated to be 69,000. Glycyrrhizan UC is composed of L-arabinose:D-galactose:D-glucose:L-rhamnose in the molar ratio of 10:30 27:1. Methylation analysis, carbon-13 nuclear magnetic resonance and periodate oxidation studies indicated its structural feature as an arabino-3,6-galacto-glucan type polysaccharide.     

Determination of phosphatidylglycerol in amniotic fluid for prediction of foetal lung maturity by microbore-column liquid chromatography

Phosphatidylglycerol (PG) has been determined in amniotic fluid from 55 patients by using a microbore-column liquid chromatographic system. The present analysis time is 1 h 40 min for pretreatment of amniotic fluid and 20 min for a chromatographic run. From 2 ml of amniotic fluid, the PG content has been determined between 1.0 and 0.05 mg/dl. The detection limit of PG is 10 ng. As the injection volume (0.5 microliter) is small, repeated analyses are possible if necessary. It is concluded that, in the case of PG values over 0.10 mg/dl, a mother can deliver an infant without respiratory distress syndrome. This method is useful not only for the prenatal evaluation of lung maturity, but also for the assessment of any therapeutic effect.     

Methionine radical cation: structural studies as a function of pH using X- and Q-band time-resolved electron paramagnetic resonance spectroscopy

A comprehensive high resolution electron paramagnetic resonance (EPR) characterization of the l-methionine radical cation and its N-acetyl derivative in liquid solution at room temperature is presented. The cations were generated photochemically in high yield by excimer laser excitation of a water soluble dye, anthraquinone sulfonate sodium salt, the excited triplet state of which is quenched by electron transfer from the side chain sulfur atom of methionine or N-acetylmethionine. The radicals were detected by continuous wave (CW) time-resolved electron paramagnetic resonance (TREPR) spectroscopy at X-band (9.5 GHz) and Q-band (35 GHz) microwave frequencies. At pH values well below the pK(a) of the protonated amine nitrogen, the cation forms a dimer with another ground-state methionine molecule through a S-S three-electron bond. In basic solution, the lone pair on the nitrogen of the amino acid is available to make an intramolecular S-N three-electron bond with the side chain sulfur atom, leading to a five-membered ring structure for the cation. When the amino acid nitrogen is unsubstituted (methionine itself), rapid deprotonation to an aminyl radical takes place at high pH values. If the nitrogen is substituted (N-acetylmethionine), the cyclic structure is observed within its electron spin relaxation time at about 1 micros. Spectral simulation provides chemical shifts (g-factors) and hyperfine coupling constants for all structures, and isotopic labeling experiments strongly support the assignments.     

Kinetics of the thermal decompositions of MC2O4 to MCO3 (M=Ca,Sr AND Ba)

The kinetics of the thermal decompositions of CaC₂O₄, SrC₂O₄ and BaC₂O₄ to their carbonates were studied by thermogravimetry at constant and at linearly increasing temperatures. Isothermally, the three oxalates decompose according to A_1.43, R_1.54 and R₁ laws, respectively. Dynamically, the decompositions of the first two oxalates proceed in a similar way as under the isothermal conditions, whereas BaC₂O₄ decomposes according to a different law.Kinetic compensation laws were established for the decomposition of CaC₂O₄ and SrC₂O₄ under both isothermal and non-isothermal conditions. Such a compensation law is considered to result if correct kinetic model functionsF () are used when the isothermal and non-isothermal decompositions are regulated by the sameF().

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Zusammenfassung Die Kinetik der thermischen Zersetzung von CaC₂O₄, SrC₂O₄ und BaC₂O₄ zu den entsprechenden Carbonaten wurde durch Thermogravimetrie bei konstanter und linear ansteigender Temperatur untersucht. Isotherm werden die drei Oxalate entsprechend A_1.43, R_1.54 bzw. R₁ zersetzt. Dynamisch verläuft die Zersetzung der ersten zwei Oxalate auf ähnlichem Wege, während BaC₂O₄ nach einem davon verschiedenem Gesetz abgebaut wird. Kinetische Kompensationsgesetze wurden sowohl unter isothermen als auch unter nicht-isothermen Bedingungen für die Zersetzung von CaC₂O₄ und SrC₂O₄ ermittelt. Ein solches Kompensationsgesetz wird als Ergebnis eines solchen Vorgehens angesehen, bei dem richtige kinetische ModellfunktionenF() benutzt werden, wenn die nicht-isothermen Zersetzungen durch die gleichenF() bestimmt sind.

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- , . , , A_1.43, R_1.54 · R₁- , . , . F() «» , F().

     

Experimental and theoretical studies on the nature of weak nonbonded interactions between divalent selenium and halogen atoms

To investigate the nature of weak nonbonded selenium...halogen interactions (Se...X interactions; X = F, Cl, and Br), three types of model compounds [2-(CH(2)X)C(6)H(4)SeY (1-3), 3-(CH(2)X)-2-C(10)H(6)SeY (4-6), and 2-XC(6)H(4)CH(2)SeY (7-9); Y = CN, Cl, Br, SeAr, and Me] were synthesized, and their (77)Se NMR spectroscopic behaviors were analyzed in CDCl(3). The gradual upfield shifts of (77)Se NMR absorptions observed for series 1-3 and 4-6 suggested that the strength of Se...X interaction decreases in the order of Se...F > Se...Cl > Se...Br. The quantum chemical calculations at the B3LYP/631H level using the polarizable continuum model (PCM) revealed that the most stable conformer for 1-3 is the one with an intramolecular short Se...X atomic contact in CHCl(3) (epsilon = 4.9) and also that the n(X) --> sigma(Se-Y) orbital interaction (E(Se...X)) can reasonably explain the order of strength for the Se...X interactions. On the other hand, the (77)Se NMR absorptions observed for series 7-9 did not shift significantly from the reference compounds (C(6)H(5)CH(2)SeY), indicating the absence of the Se...X interaction for 7-9 presumably due to attenuation of basicity for the halogen atom that is substituted directly to the aromatic ring. These observations suggested that the n(X) --> sigma(Se-Y) orbital interaction is a dominant factor for formation of weak Se...X interactions. Electron correlation was also suggested to be important for the stability.     

PHOTOCHEMISTRY OF ACETYLENIC KETONES IN MICELLAR SOLUTIONS AS STUDIED BY PRODUCT-YIELD-DETECTED ESR AND TRANSIENT ABSORPTION TECHNIQUES

The electron spin resonance (ESR) spectra of the transient radical pairs in the photoreduction of 1,5-diphenyl-1,4-pentadiyn-3-one ( I ) and 1,3-diphenyl-2-propyn-1-one ( II ) in sodium dodecyl sulfate (SDS) micellar solutions have been obtained by using the product-yield-detected ESR (PYESR) technique. The PYESR spectra, detected by tracing the microwave effect on the spin-adduct yield as functions of the magnetic field, show the ESR spectra of the ketyl radical of the ketone and SDS radical as the components of the radical pairs. In addition, the growth and the decay processes of the radical pair were observed through detecting the effect of microwave pulse as functions of the delay period between a laser pulse and the off and on time, respectively, of a microwave pulse. The absorption spectra of transient species have also been obtained by using the laser flash photolysis technique. Through the analysis of these data and molecular orbital calculations, the role of acetylenic groups in the photoreactivity of acetylenic ketones is discussed.