Stereoselective reduction of α-substituted β-keto esters by hydrostannane/organotin triflate

Stereoselective reduction of α-substituted β-keto esters is achieved by the combined use of hydrostannane/organotin triflate. syn-Aldols are obtained with more than 90% selectivities.     

Chiral separation of cathinone derivatives using β‐cyclodextrin‐assisted capillary electrophoresis–Comparison of four different β‐cyclodextrin derivatives used as chiral selectors

In the past decade, more than 100 different cathinone derivatives slopped over entire Europe due to their enormous popularity. Generally, these novel psychoactive substances are easily available via the internet. This fact leads to various social problems, since cathinones are substances with consciousness‐changing effects and are mainly misused for recreational matters by their consumers. Cathinones possess a chiral center including two enantiomeric forms with potentially different pharmacological behavior. This fact makes analytical method development regarding their chiral separation indispensable. In this study, a chiral capillary zone electrophoresis method for the enantioseparation of 61 cathinone and pyrovalerone derivatives was developed by means of four different β‐cyclodextrin derivatives. As chiral selectors, native β‐cyclodextrin as well as three of its derivatives namely acetyl‐β‐cyclodextrin, 2‐hydroxypropyl‐β‐cyclodextrin, and carboxymethyl‐β‐cyclodextrin were used. The cathinone and pyrovalerone derivatives were either purchased in internet stores or seized by police. As a result, overall 58 of 61 studied substances were partially or baseline separated by at least one of the four chiral selectors using 10 mM of β‐cyclodextrin derivative in a 10 mM sodium phosphate buffer (pH 2.5). Furthermore, the method was found to be suitable for simultaneous enantioseparations, for enantiomeric purity checks and to differentiate between positional isomers. Moreover, an intra‐ and an interday validation was performed successfully for each chiral selector to prove the robustness of the method.     

Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet

Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s⁻¹) and high (1800 s⁻¹) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIbα deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s⁻¹). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.     

Synthesis of β‐Haloketones by β‐Addition Reactions of α,β‐Unsaturated Ketones with BX3 (X = Br,Cl) as Halide Source

A series of β‐bromoketones and β‐chloroketones were synthesized by the addition reactions of α,β‐unsaturated ketones under BX₃ (X = Br, Cl) and ethylene glycol reaction system. The α,β‐unsaturated ester also was successfully converted to its corresponding β‐bromoester under the reaction condition.     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

Photoinduced transformation of α,β-epoxyketones to β-hydroxyketones by Hantzsch 1,4-dihydropyridine

Irradiation (λ >300 nm) of Hantzsch 1,4-dihydropyridine with aromatic α,β-epoxyketones in acetonitrile selectively breaks the Cα---O bond of the epoxides giving the corresponding β-hydroxyketones in excellent yields.     

Separation of α‐ from β‐arylalanines by nickel nitrilotriacetate chromatography

A method is described to separate α‐ from β‐arylalanines by ligand exchange chromatography on a nickel nitrilotriacetate agarose column with UV monitoring of the effluent. Separate mixtures containing an α‐ and β‐arylalanine pair (1 mg of each) were individually loaded onto the nickel resin pre‐equilibrated with the mobile phase at room temperature, and the amino acids were eluted from the column with a gradient from pH 12.0–8.0. The β‐arylalanines eluted first, followed by the α‐isomers. The four α/β‐amino acid pairs tested were well separated with baseline resolution. An aliquot of each fraction was chemically treated to derivatize the amino acids to their N‐acyl methyl ester analogs, and their identities were confirmed by GC/MS analysis. The sample recovery was quantitative (>98%), and the column matrix was very resilient, as demonstrated by consistent separation of the solutes after ～100 preparative cycles.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

Synthesis of Halogenated α,β‐Unsaturated γ‐Butyrolactone Derivatives by Triphenylphosphine‐Catalyzed Cyclization of α‐Halogeno Ketones with Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates)

A Ph₃P‐catalyzed cyclization of α‐halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 3 produced halogenated α,β‐unsaturated γ‐butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electron‐withdrawing groups such as halogen atoms at the α‐position of the ketones was necessary in this reaction. Cyclization of α‐chloro ketones resulted in higher yields than that of the corresponding α‐bromo ketones. Dihalogeno ketones similarly afforded the expected γ‐butyrolactone derivatives in high yields.     

New single isomer negatively charged β‐cyclodextrin derivatives as chiral selectors in capillary electrophoresis

To improve resolution power of chiral selector and enantiomeric peak efficiency in CE, single isomer negatively charged β‐CD derivatives, mono(6‐deoxy‐6‐sulfoethylthio)‐β‐CD (SET‐β‐CD) bearing one negative charge and mono[6‐deoxy‐6‐(6‐sulfooxy‐5,5‐bis‐sulfooxymethyl)hexylthio]‐β‐CD (SMHT‐β‐CD) carrying three negative charges, were synthesized. The structure of these two β‐CD derivatives was confirmed by ¹H NMR and MS. SET‐β‐CD and SMHT‐β‐CD successfully resolved the enantiomers of several basic model compounds. SMHT‐β‐CD provided for a significantly greater enantioseparation than SET‐β‐CD at lower concentrations. This appears to be due to the higher binding affinity of SMHT‐β‐CD to the model compounds and the wider separation window resulting from an increased countercurrent mobility of the selector. Overall, the new chiral selectors provided enantioseparations with high peak efficiency while avoiding peak distortion due to polydispersive and electrodispersive effects. The information obtained from an apparent binding constant study suggested that the enantioseparation of the model compounds followed the predictions of charged resolving agent migration model and that the observed degree of enantioseparation difference were due to the magnitude of differences in both enantiomer‐chiral selector binding affinities (ΔK) and the mobilities of the complexed enantiomers (Δμ_c).     

Reactions of 3, 5-Dimethyl-4-Carbethoxy-2-Cyclohexen-1-One at α-Position

3, 5-Dimethyl-4-carbethoxy-2-cyclohexen-1-one has been synthesized through the Knoevenagel condensation¹, which is then subjected to alkylation and acylation at α-position. The resulting products are hydrolyzed and decarboxylated to α-substituted cyclohexenones. 3, 5-Dimethyl-2-cyclohexen-1-one is converted by N-bromosuccinimide to phenol via enolization².     

Synthesis of β‐Hydroxy α‐Sulfanyl Esters by Using Nanocrystalline Magnesium Oxide

Aldol‐type reaction between electron deficient aldehydes and sulfonium salts to afford the corresponding β‐hydroxy α‐sulfanyl esters in moderate‐to‐good yields by using nanocrystalline MgO is described. The sulfanyl group is a useful group for further transformations in organic synthesis. Low R_f‐value isomer is anti‐configured as revealed by X‐ray diffraction study and consistent with the assignment of ¹H‐NMR spectrum.     

Detection of β-blocking drugs in urine by capillary column gas chromatography-negative ion chemical ionization mass spectrometry

β-Blocking drugs present in commercial pharmaceutical products are determined in present urine of volunteers between 4 and 24 hours after the administration of a therapeutical dose. The drugs are extracted, hydrolysed, derivatized with pentafluoropropionic anhydride, and analyzed by capillary gas chromatography and electron capture detection. Metabolite identification and drug confirmation is by capillary gas chromatography–negative ion chemical ionization mass spectrometry (GC-NICIMS). This method is very specific and a sensitivity below 1 ng/ml is obtained.     

Palladium‐catalyzed carbonylative cyclization of β‐bromo‐α,β‐unsaturated carboxylic acids with primary amines leading to N‐alkylmaleimides

Cyclic β‐bromo‐α,β‐unsaturated carboxylic acids are carbonylatively cyclized with primary amines under carbon monoxide pressure in MeCN in the presence of a catalytic amount of PdCl₂(PPh₃)₂ to give N‐alkylmaleimides. Copyright © 2012 John Wiley & Sons, Ltd.     

Preparation,characterization and properties of β-chitin and N-acetylated β-chitin

Free amino groups in β-chitin from squid pen were acetylated to obtain N-acetylated β-chitin. After careful control of degree of acetylation, thermal and mechanical properties of β-chitin and N-acetylated β-chitin were compared. The structural differences of β-chitin and N-acetylated β-chitin were characterized by Fourier transform infrared (FTIR) and wide-angle x-ray diffraction (WAXD) analysis. The results indicated that the crystallinity of N-acetylated β-chitin was higher than that of β-chitin and N-acetylated β-chitin exhibited characteristics similar to α-chitin. Equilibrium water content (EWC) of β-chitin reached to about 50% and this hydrophilic nature was assumed to be caused by a relatively weak hydrogen bonding force of β-chitin with parallel main chains. On the other hand, EWC of N-acetylated β-chitin was 40% due to the introduction of ordered structure. β-chitin and N-acetylated β-chitin have the tensile strength of 0.4 and 0.7 Mpa in the swollen state, respectively. Viscoelastic properties and thermal relaxation behaviors were investigated by dynamic mechanical thermal analysis (DMTA). DMTA spectra of these samples showed that α-transition peaks of β-chitin and N-acetylated β-chitin were observed at 170 and 190°C, respectively. These relaxation peak maxima were assigned to be their glass transition temperature. In addition, a second relaxation peak of β-chitin resulting from acetamide groups was found at 112°C and a broad relaxation peak of N-acetylated β-chitin at around 81–100°C. As a result of thermogravimetric analysis, 10% weight loss temperatures of β-chitin and N-acetylated β-chitin were 270 and 285°C, respectively. © 1996 John Wiley & Sons, Inc.     

Stable Peptides Instead of Stapled Peptides: Highly Potent αvβ6‐Selective Integrin Ligands

The αvβ6 integrin binds the RGD‐containing peptide of the foot and mouth disease virus with high selectivity. In this study, the long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub‐nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins. Computational studies were performed to disclose the molecular bases underlying the high binding affinity and receptor subtype selectivity of this peptide. Finally, the utility of the ligand for use in biomedical studies was also demonstrated here.