(S)-selective dynamic kinetic resolution of secondary alcohols by the combination of subtilisin and an aminocyclopentadienylruthenium complex as the catalysts

A new procedure for the dynamic kinetic resolution (DKR) of racemic alcohols into single enantiomers is described. This procedure employs surfactant-treated subtilisin as an (S)-selective resolving catalyst and an aminocyclopentadienylruthenium complex as a racemizing catalyst. The DKR is performed best in the presence of an acyl donor such as trifluoroethyl butyrate in THF at room temperature. Eight simple secondary alcohols have been efficiently resolved with high optical purities and good yields. The subtilisin-based DKR is complementary in stereoselectivity to its lipase-based counterpart. For an acyl-carrying alcohol, both subtilisin- and lipase-based DKRs have proceeded equally well to give a pair of enantiomeric products (>99.5% ee each) with opposite optical rotations in high yields (94-95%).     

On the stereological estimation of reduced moment measures

Recently, a new set of fundamental stereological formulae based on isotropically oriented probes through fixed points have been derived, the so-called nucleator estimation principle (cf. Jensen and Gundersen (1989, J. Microsc., 153, 249–267)). In the present paper, it is shown how a model-based version of these formulae leads to stereological estimators of reduced moment measures of stationary and isotropic random sets in ⁿ .     

Controlling degradation of acid-hydrolyzable pluronic hydrogels by physical entrapment of poly(lactic acid-co-glycolic acid) microspheres

Chemically crosslinked biodegradable hydrogels based on di-acrylated Pluronic F-127 tri-block copolymer were prepared by a photopolymerization method. Poly(lactic acid-co-glycolic acid) (PLGA) microspheres were physically entrapped within the Pluronic hydrogel in order to modulate the local pH environment by acidic degradation by-products of PLGA microspheres. The PLGA microspheres were slowly degraded to create an acidic microenvironment, which facilitated the cleavage of an acid-labile ester-linkage in the biodegradable Pluronic hydrogel network. The presence of PLGA microspheres accelerated the degradation of the Pluronic hydrogel and enhanced the protein release rate when protein was loaded in the hydrogel.SEM image of photo-crosslinked Pluronic hydrogel entrapping PLGA microspheres.     

Diastereoselective synthesis of syn-aminoalcohols via contributing CH-π interaction: simple synthesis of (−)-bestatin

¹H NMR and X-ray crystallography studies revealed that a CH-π and chelation control in aromatic aminoaldehydes (1-6) effects a highly diastereoselective addition to afford optically active syn-aminoalcohols (1a-6a). This methodology was applied to the synthesis of (−)-bestatin.     

Nucleophilic substitution reactions of alpha-chloroacetanilides with benzylamines in dimethyl sulfoxide

Kinetic studies of the reactions of alpha-chloroacetanilides (YC6H4NRC(=O)CH2Cl; R = H (5) and CH3 (6)) with benzylamines (NH2CH2C6H4X) were carried out in dimethyl sulfoxide at 55.0 degrees C. The Br?nsted betaX values were in the range from 0.6 to 0.9 and cross-interaction constants phoXY were positive: phoXY = +0.21 and +0.18 for 5 and 6, respectively. The rates were faster with 6 than with 5 and inverse secondary kinetic isotope effects involving deuterated benzylamine (ND2CH2C6H4X) nucleophiles, kH/kD < 1.0, were obtained. Based on these and other results, a stepwise mechanism with rate-limiting expulsion of the chloride leaving group from a zwitterionic tetrahedral intermediate, T+/-, is proposed. In this mechanism, a prior carbonyl addition to T+/- is followed by a bridged type transition state to expel the chloride. An enolate-like transition state in which the developing negative charge on C(alpha) delocalizes toward the carbonyl group (nC-->pi*(C=O) interaction) is not feasible for the present series of reactions due to a stronger charge transfer involving the lone pair on the anilino nitrogen (nAN-->pi*(C=O) interaction).     

Spermidine attenuates bleomycin-induced lung fibrosis by inducing autophagy and inhibiting endoplasmic reticulum stress (ERS)-induced cell death in mice

Spermidine is an endogenous biological polyamine that plays various longevity-extending roles and exerts antioxidative, antiaging, and cell growth-promoting effects. We previously reported that spermidine levels were significantly reduced in idiopathic pulmonary fibrosis (IPF) of the lung. The present study assessed the potential beneficial effects of spermidine on lung fibrosis and investigated the possible mechanism. Lung fibrosis was established in mice using bleomycin (BLM), and exogenous spermidine was administered daily by intraperitoneal injection (50 mg/kg in phosphate-buffered saline). BLM-induced alveolar epithelial cells showed significant increases in apoptosis and endoplasmic reticulum stress (ERS)-related mediators, and spermidine attenuated BLM-induced apoptosis and activation of the ERS-related pathway. Senescence-associated β-gal staining and decreased expression of p16 and p21 showed that spermidine ameliorated BLM-induced premature cellular senescence. In addition, spermidine enhanced beclin-1-dependent autophagy and autophagy modulators in IPF fibroblasts and BLM-induced mouse lungs, in which inflammation and collagen deposition were significantly decreased. This beneficial effect was related to the antiapoptotic downregulation of the ERS pathway, antisenescence effects, and autophagy activation. Our findings suggest that spermidine could be a therapeutic agent for IPF treatment.Subject terms: Immunology, Diseases     

Controlled re-oxidation of low-pressure methanol synthesis catalyst,followed by means of DSC

The re-oxidation of low-pressure methanol synthesis catalyst was followed by means of DSC, with the aim of contributing to a better understanding of the processes taking place during catalyst blanketing, stabilization and re-oxidation. The investigations were carried out with previously hydrogen-reduced samples, and their successive re-oxidation was performed with different oxygen contents in the oxygen/nitrogen gas mixtures. A procedure for catalyst stabilization and/or catalyst discharge is proposed.     

Synthesis and bioactivities of steroid derivatives as antifungal agents

A series of lanosterol and cholesterol derivatives with modified side chain structures, which might interfere with sterol C24-methyltransferase in the ergosterol biosynthesis as substrate analogs, have been synthesized. The in vitro bioassay studies have shown that some of these compounds, in particular with C24-amino- and thio-functionalities, possess potent antifungal activities, in vivo. Bioassays have also been carried out for the leading compounds.