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.     

Synthesis and biological properties of 4‐substituted quinolin‐2(1H)‐one analogues

A variety of 4‐substituted quinolin‐2(1H)‐ones were prepared and evaluated for N‐methyl‐D‐aspar‐tate (NMDA) receptor binding site activity and their abilities to inhibit neurotoxicity. The 4‐(2‐car‐bethoxyethanamino)‐7‐chloro‐3‐nitroquinolin‐2(1H)‐one ( 9b ) exhibited favorable NMDA receptor binding site activity and 7‐chloro‐4‐(benzylamino)‐3‐nitroquinolin‐2(1H)‐one ( 9c ) showed the most potent neurotoxicity among them. The synthetic strategies involve the use of well known keto ester condensation and reductive ring cyclization of intermediates ( 2a‐d ) to afford 4‐substituted quinolin‐2(1H)‐ones.     

Loss of trace impurities during NAA of liquid reagents

The loss of trace elements during NAA of five liquid reagents, hydrofluoric acid, hydrochloric acid, nitric acid, hydrogen peroxide and deioniyed water, has been investigated using 17 radioactive tracers of⁴⁶Sc,⁵¹Cr,⁵⁴Mn,⁵⁹Fe,⁶⁰Co,⁶⁴⁵Zn,⁷⁵Se,⁸⁵Sr,⁹⁵Zr,¹¹³Sn,¹²⁴Sb,¹⁵¹Eu,¹⁶⁰Yb,¹⁷⁷Lu,¹⁸²Ta,²³³Pa. Two kinds of container quartz and polyethylene have been used for irradiation and also for preconcentration of the reagents. The containers were cleaned before use by washing-leaching-rinsing procedure. The reagents were preconcentrated by subboiling evaporation under the infrared lamp in clean bench. The loss of trace elements has been revealed to be severer for the reagents of hydrochloric acid and nitric acid in the container of quartz than for the other cases, while that is lowest for hydrogen peroxide.     

Synthesis and characterization of soluble aromatic polyurea-amides from new N,N′--dimethyl-N,N′-bis(aminophenyl)ureas and aromatic dicarboxylic acid chlorides

Aromatic polyurea-amides having inherent viscosities of 0.36–0.67 dL/g were synthesized by the low temperature solution polycondensation of new N,N′-dimethyl-N,N′-bis(aminophenyl)ureas with various aromatic dicarboxylic acid chlorides. All the polymers were amorphous, and most of them were soluble in a variety of organic solvents such as N-methyl-2-pyrrolidone, N,N-dimethylacetamide (DMAc), m-cresol, and pyridine. Some of the polymers could be cast from the DMAc solutions into transparent and flexible films having good tensile properties. The glass transition temperatures of the polyurea-amides obtained from the bis(4-aminophenyl)-substituted ureas were 244–272°C. The temperatures of 10% weight loss under nitrogen of the polymers were in the range of 430 and 480°C. © 1995 John Wiley & Sons, Inc.     

Alterations of HLA class I and class II antigen expressions in borderline, invasive and metastatic ovarian cancers

In an effort to understand whether HLA class I and II plays any role in the process of tumorigenesis and metastasis, we have immunohistochemically examined expression of HLA class I and II antigen by using the monoclonal antibodies (mAb) L368 (for beta2m of HLA class I), HC-10 (for HLA-B, C heavy chains), and LGII-612.14 (for HLA class II heavy chain) in 5 borderline serous malignancy (BSM), 20 serous adenocarcinomas (SA), 15 borderline mucinous malignancy (BMM), and 10 mucinous adenocarcinomas (MA) of human ovary tumor case tissues. In BSM, the distribution and intensity of HLA expressions failed to reach statistical significance. In SA, HLA class I beta2-microglobulin (beta2m), HLA-B, C heavy chains and HLA class II heavy chain antigen expressions were down-regulated. Although expressions of HLA-B, C heavy chains and class II heavy chain were down-regulated in metastatic SA, there were no differences in HLA expression levels between primary and metastatic lesions. In BMM, class II heavy chain expressions were down-regulated. In MA, beta2m, HLA-B, C heavy chains and class II heavy chain expressions were also down-regulated. Thus, we could distinguish the reduction or absence of HLA molecule expression was related to malignant potential. Loss of HLA class I and II molecules in invasive ovarian cancers raises the possibility that this could be a factor for tumor cells to retain invasiveness.