Stereoselective Lewis Base‐Catalyzed Asymmetric Hydrosilylation of α‐Acetamido‐β‐enamino Esters: Straightforward Approach for the Construction of α,β‐Diamino Acid Derivatives

The Lewis base‐organocatalyzed asymmetric hydrosilylation of α‐acetamido‐β‐enamino esters was investigated. Among various chiral Lewis base catalysts, a novel catalyst derived from L ‐serine was found to be the most efficient one which can promote the reaction to afford a series of α,β‐diamino acid derivatives with high yields (up to 99%), excellent enantioselectivities (up to 98% ee) and moderate diastereoselectivities (up to 80:20 dr). The absolute configuration of one of the products was determined by the X‐ray crystallographic analysis. In addition, the mechanism and the transition state of the reaction were proposed.     

Synthesis of Functionalized Indolizines by Lewis Acid‐Mediated Cyclocondensation of 3‐(Pyridin‐2‐yl)‐propiolates with Enones

Functionalized indolizines were prepared by Lewis acid‐catalyzed cyclizations of 3‐(pyridin‐2‐yl)‐propiolates with enones. This new type of reaction provides a convenient and regioselective approach to ester‐substituted indolizine derivatives which are not readily available by other methods. Based on density function theory (DFT) calculations, a mechanism of the reaction has been suggested.     

Direct Synthesis of Partially Modified 2′‐O‐Pivaloyloxymethyl RNAs by a Base‐Labile Protecting Group Strategy and their Potential for Prodrug‐Based Gene‐Silencing Applications

An original and straightforward synthesis of partially modified 2′‐O‐pivaloyloxymethyl‐substituted (PivOM‐substituted) oligoribonucleotides has been achieved. The aim of this 2′‐enzymolabile modification was to enhance nuclease stability of RNA and transmembrane transport. To make these modified RNAs easily available we developed a base‐labile protecting group strategy with standard protections for nucleobases (acyl) and phosphates (cyanoethyl), a Q‐linker and two different acetalester protection groups for 2′‐OH: propionyloxymethyl (PrOM) and PivOM. Interestingly, orthogonal deprotection conditions based on anhydrous butylamine in THF were found to remove propionyloxymethyl groups selectively, while preserving PivOM groups. Duplex stability, circular dichroism studies and nuclease resistance, as well as the ability to inhibit gene expression of modified 2′‐O‐PivOM RNA, were evaluated.     

Synthesis of 2‐(9H‐carbazole‐9‐yl)ethyl methacrylate: Electrochemical impedance spectroscopic study of poly(2‐(9H‐carbazole‐9‐yl)ethyl methacrylate) on carbon fiber

In this contribution, 2‐(9H‐carbazol‐9‐yl) ethyl methacrylate (CzEMA) monomer was chemically synthesized. The monomer characterization was performed by FT‐IR, ¹H‐NMR, ¹³C‐NMR, and melting point analysis. The electropolymerization of CzEMA was studied onto carbon fiber microelectrodes (CFMEs) as an active electrode material in 0.1M sodium perchlorate (NaClO₄)/acetonitrile (ACN) solution. The electropolymerization experiments were done from 1 mM to 10 mM. The detailed characterization of the resulting electrocoated Poly (CzEMA)/CFME thin films was studied by various techniques, i.e., cyclic voltammetry (CV), Scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The effects of initial monomer concentrations (1, 3, 5, and 10 mM) during the preparation of modified electrodes were examined by EIS. Capacitive behaviors of modified CFMEs were defined via Nyquist, Bode‐magnitude, and Bode‐phase plots. Variation of capacitance values by initial monomer concentration and specific capacitance values are presented. The highest specific capacitance value electrocoated polymer thin film by CV method in the initial monomer concentration of 5 mM with a charge of 52.74 mC was obtained about 424.1 μF cm^?2. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Diversified Construction of Chromeno[3,4‐c]pyridin‐5‐one and Benzo[c]chromen‐6‐one Derivatives by Domino Reaction of 4‐Alkynyl‐2‐oxo‐2H‐chromene‐3‐carbaldehydes

Silver‐catalyzed three‐component, tandem reactions of 4‐alkynyl‐2‐oxo‐2H‐chromene‐3‐carbaldehydes, amines and various nucleophiles result in the formation of highly functionalized chromeno[3,4‐c]pyridin‐5‐ones in high yields. Gold‐catalyzed [4+2] cycloadditions of 4‐alkynyl‐2‐oxo‐2H‐chromene‐3‐carbaldehydes with alkynes or alkenes have also been achieved to afford benzo[c]chromen‐6‐ones efficiently.

     

Effect of ZnCl2‐ and SiCl4‐doped TiCl4/MgCl2/THF catalysts for ethylene polymerization

In this research, ethylene polymerization was carried out in the presence of different additives (ZnCl₂, SiCl₄, and the combined ZnCl₂‐SiCl₄) on TiCl₄/MgCl₂/THF catalytic system. The presence of ZnCl₂‐SiCl₄ mixtures showed higher activity in ethylene polymerization when compared with the catalytic activity in the presence of single Lewis acids, ZnCl₂, or SiCl₄. The modified catalyst with ZnCl₂‐SiCl₄ demonstrated the highest activity, which was more than three times the activity of the system without Lewis acid modification. The enhanced activity can be attributed to the reduction in the peak intensity of MgCl₂/THF complexes with Lewis acid compounds as proven by XRD. This was reasonable because of some THF removal from the structure of MgCl₂/THF by Lewis acid compounds. In addition to the effect of modification with additives on the partial elimination of THF, the catalytic activities could be increased due to the titanium atoms that have been locally concentrated on the surface as seen by energy dispersive X‐ray spectroscopy measurement. On the basis of the in situ electron spin resonance measurement, the mixed metal chlorides (ZnCl₂‐SiCl₄) addition could promote the amount of Ti³⁺after reduction with triethylaluminum. It revealed that the modification of TiCl₄/MgCl₂/THF catalytic system with mixed metal chlorides (ZnCl₂‐SiCl₄) is very useful for ethylene polymerization. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1588–1594, 2013     

Synthesis of 9‐(4‐nitrophenylsulfonyl)‐9H‐carbazole: Comparison of an impedance study of poly[9‐(4‐nitrophenylsulfonyl)‐9H‐carbazole] on gold and carbon fiber microelectrodes

In this study, 9‐(4‐nitrophenylsulfonyl)‐9H‐carbazole (NPhSCz) monomer was chemically synthesized. The monomer characterization was performed by Fourier transform infrared spectroscopy, ¹H‐NMR, and melting point analysis. Two different electropolymerizations of NPhSCz were studied on a gold microelectrode (Au electrode) and carbon fiber microelectrodes (CFMEs) in a 0.1M sodium perchlorate (NaClO₄)/acetonitrile solution. The electropolymerization experiments were done from 1 to 4 mM. The characterizations of two different modified electrodes of poly[9‐(4‐nitrophenylsulfonyl)‐9H‐carbazole] [poly(NPhSCz)] were performed by various techniques, including cyclic voltammetry, scanning electron microscopy–energy‐dispersive X‐ray analysis, and electrochemical impedance spectroscopy (EIS). The effects of the initial monomer concentrations (1, 2, 3, and 4 mM) were examined by EIS. The capacitive behaviors of the modified electrodes were defined via Nyquist, Bode magnitude, Bode phase, and admittance plots. The variation of the low‐frequency capacitance (C_LF) and double‐layer capacitance (C_dl) values are presented at different initial monomer concentrations. Poly(NPhSCz)/CFME was more capacitive (C_LF = 6.66 F/cm² and C_dl ≈ 28 mF) than the Au electrode (C_LF = 6.53 F/cm² and C_dl ≈ 20 mF). An equivalent circuit model of R[QR(CR)(RW)](CR), (R: Current, Q: Constant phase element, C: Double layer capacitance, W: Warburg impedance), was used to fit the theoretical and experimental data. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

5′‐Trityl‐Substituted Thymidine Derivatives as a Novel Class of Antileishmanial Agents: Leishmania infantum EndoG as a Potential Target

Two series of 5′‐triphenylmethyl (trityl)‐substituted thymidine derivatives were synthesized and tested against Leishmania infantum axenic promastigotes and amastigotes. Several of these compounds show significant antileishmanial activity, with IC₅₀ values in the low micromolar range. Among these, 3′‐O‐(isoleucylisoleucyl)‐5′‐O‐(3,3,3‐triphenylpropanoyl)thymidine displays particularly good activity against intracellular amastigotes. Assays performed to characterize the nature of parasite cell death in the presence of the tritylthymidines indicated significant alterations in mitochondrial transmembrane potential, an increase in superoxide concentrations, and also significant decreases in DNA degradation during the cell death process. Results point to the mitochondrial nuclease LiEndoG as a target for the action of this family of compounds.     

Chiral Lewis Base‐Catalyzed,Enantioselective Reduction of Unprotected β‐Enamino Esters with Trichlorosilane

Catalytic asymmetric reduction of N‐unsubstituted β‐enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N‐unsubstituted β‐enamino esters has been developed. Using N‐tert‐butylsulfinyl‐L ‐proline‐derived amides and L ‐pipecolinic acid‐derived formamides as catalyst, a broad range of β‐aryl‐ and β‐alkyl‐substituted free β‐amino esters could be prepared with high yields and enantioselectivities. The practicality was illustrated by the gram‐scale asymmetric synthesis of ethyl (R)‐3‐amino‐3‐phenylpropanoate and isopropyl (S)‐3‐amino‐4‐(2,3,5‐trifluorophenyl)butanoate. The resulting product can be smoothly transformed to the FDA approved medicines dapoxetine and sitagliptin in a short synthetic route.

     

Convenient Synthesis of (E)‐5‐Aryl(halo)methylenebicyclo‐ [2.2.2]oct‐2‐enes and ‐[2.2.1]hept‐2‐enes via Lewis Acid‐ Promoted Carbohalogenation of Cyclic 2,6‐Enynols

An efficient synthesis of (E)‐5‐aryl(halo)methylenebicyclo[2.2.2]oct‐2‐enes is reported. Lewis acid‐promoted carbohalogenation of 4‐(3‐arylprop‐2‐ynyl)‐cyclohex‐2‐enols in dichloromethane proceeds rapidly to afford the exo‐methylene‐bridged bicycles in good yields. This method also provides an easy access to (E)‐5‐aryl(halo)methylenebicyclo[2.2.1]hept‐2‐enes from the five‐membered ring 2,6‐enynols. The reactions are procedurally simple and high yielding, producing the aryl(halo)methylene‐bridged bicycles in minutes under air and mild conditions.

     

Organosoluble and light‐colored fluorinated polyimides based on 2,2‐bis[4‐(4‐amino‐2‐trifluoromethylphenoxy)phenyl]propane and aromatic dianhydrides

A novel fluorinated diamine monomer, 2,2‐bis[4‐(4‐amino‐2‐trifluoromethylphenoxy)phenyl]propane (2), was prepared through the nucleophilic substitution reaction of 2‐chloro‐5‐nitrobenzotrifluoride with 2,2‐bis(4‐hydroxyphenyl)propane in the presence of potassium carbonate, followed by catalytic reduction with hydrazine and Pd/C. Polyimides were synthesized from diamine 2 and various aromatic dianhydrides 3a–f via thermal imidization. These polymers had inherent viscosities ranging from 0.73 to 1.29 dL/g. Polyimides 5a–f were soluble in amide polar solvents and even in less polar solvents. These films had tensile strengths of 87–100 MPa, elongations to break of 8–29%, and initial moduli of 1.7–2.2 GPa. The glass transition temperatures (T_g) of 5a–f were in the range of 222–271°C, and the 10% weight loss temperatures (T₁₀) of them were all above 493°C. Compared with polyimides 6 series based on 2,2‐bis[4‐(4‐aminophenoxy)phenyl]propane (BAPP) and polyimides 7 based on 2,2‐Bis[4‐(4‐aminophenoxy)phenyl]hexafluoropropane (6FBAPP), the 5 series showed better solubility and lower color intensity, dielectric constant, and lower moisture absorption. Their films had cutoff wavelengths between 363 and 404 nm, b* values ranging from 8 to 62, dielectric constants of 2.68–3.16 (1 MHz), and moisture absorptions in the range of 0.04–0.35 wt %. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 922–935, 2005     

Organosoluble and light‐colored fluorinated polyimides derived from 5,5′‐bis[4‐(4‐amino‐2‐trifluoromethylphenoxy) phenyl]‐4,7‐methanohexahydroindan

A novel bis(ether amine) monomer, 5,5′‐bis[4‐(4‐amino‐2‐trifluoromethylphenoxy)phenyl]‐4,7‐methanohexahydroindan ( 2 ), was synthesized through the nucleophilic aromatic substitution reaction of 5,5′‐bis‐(4‐hydroxyphenyl)‐4,7‐methanohexahydroindan with 2‐chloro‐5‐nitrobenzotrifluoride to yield the intermediate dinitro compound, followed by catalytic reduction with hydrazine and Pd/C. A series of polyimides were synthesized from 2 and various aromatic dianhydrides using a standard two‐stage process with chemical or thermal imidization of poly(amic acid). All of these polymer films were soluble in amide‐type solvents above 10% w/v, had tensile strengths of 97–117 MPa, and the 10% weight loss temperature was above 464 °C with their residues exceeding 46% at 800 °C in nitrogen. Compared with the non‐fluorinated polyimides, the fluorinated series were observed to have lower dielectric constants (2.92–3.28 at 1 MHz) and lower moisture absorptions (0.15–0.43 wt%) as well as lower color intensity and better solubility. Copyright © 2006 Society of Chemical Industry     

Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands

Inhibition of adenosine A_2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A_2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A_2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A_2AR (K_i=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours).     

Stereocontrolled synthesis of the taxol C‐13 side chain: Methyl (2R,3S)‐3‐benzoylamino‐2‐hydroxy‐3‐phenylpropanoate

Addition of lithiated methoxyallene 5 to literature‐known amino aldehyde 3 followed by ozonolysis provided syn‐configurated α‐hydroxy‐β‐amino ester 6 in moderate overall yield and with an ee of 90%. The predominant formation of syn‐compounds may be due to a chelate controlled addition step.     

Novel building blocks for oligonuclear copper complexes derived from β‐ketoenamines of histidine

Condensation products of L‐histidine with the 3‐oxoenolethers diethyl‐ethoxymethylene‐malonate ( 1 ) and ethyl‐ethoxymethylene‐cyanoacetate ( 2 ) react with copper(II) as di‐anionic ligands to give neutral 1:1 complexes Cu‐ His1 and Cu‐ His2 . Both complexes crystallize as oligonuclear units, even from strongly donating solvents like N‐methylimidazole (Meim) (Cu‐ His1 ) and pyridine (Cu‐ His2 ). X‐ray structure analyses show supramolecular structures, formed of two (Cu‐ His1 ) or four (Cu‐ His2 ) formula units of the complex, which arrange to macrocycles by means of intermolecular coordination of the imidazole‐N. Strong H‐bridges result in a face‐to‐face orientation of the hydrophilic sites of two great rings. ESI‐MS investigations in pyridine solution give evidence for the existence of dimeric, tetrameric and – in case of Cu‐ His2 – trimeric units, besides the monomeric adducts with one pyridine. In contrast to the dimeric or tetrameric (“cubane‐like”) copper(II) complexes of amino alcohols and their β‐ketoenamines, the complexes Cu‐ His1 and Cu‐ His2 show no significant spin coupling from room temperature down to 4 K. The complexes Cu‐ His1 and Cu‐ His2 give no electrochemically reversible Cu^II/I reduction in pyridine. However, the isolation of a stable diamagnetic copper(I) complex of the methylester derivative, Cu^I‐ HisMe1 , supports the assumption, that similar histidine‐derived copper complexes should display reversible redox behaviour and catalytic activity in reactions with O₂.     

3,5‐Bis(n‐perfluorooctyl)benzyltriethylammonium Bromide (F‐TEBA): An Efficient,Easily Recoverable Fluorous Catalyst for Solid‐Liquid PTC Reactions

A readily available 3,5‐bis(perfluorooctyl)benzyl bromide and triethylamine were reacted under mild conditions to give 3,5‐bis(n‐perfluorooctyl)benzyltriethylammonium bromide ( F‐TEBA ), an analogue of the versatile phase‐transfer catalyst, benzyltriethylammonium chloride (TEBA), containing two fluorous ponytails. This perfluoroalkylated quaternary ammonium salt was successfully employed as a catalyst in a variety of reactions run under solid‐liquid phase‐transfer catalysis (SL‐PTC) conditions. Thus, being both hydrophobic and lipophobic, F‐TEBA could be quickly recovered in quantitative yields, and reused without loss of activity over several reaction cycles.     

Chiral Octahedral Complexes of Cobalt(III) as “Organic Catalysts in Disguise” for the Asymmetric Addition of a Glycine Schiff Base Ester to Activated Olefins

Stereochemically inert and positively charged chiral complexes of cobalt(III) prepared from Schiff bases derived from chiral diamines and salicylaldehydes were shown to be efficient catalysts of the benchmark asymmetric phase‐transfer Michael addition of nine activated olefins to O’Donnell’s substrate. The reaction products had enantiomeric purities of up to 96%. DFT calculations were invoked to rationalize the stereochemistry of the addition.

     

Chemistry and Pharmacology of Nicotinic Ligands Based on 6‐[5‐(Azetidin‐2‐ylmethoxy)pyridin‐3‐yl]hex‐5‐yn‐1‐ol (AMOP‐H‐OH) for Possible Use in Depression

AMOP‐H‐OH (sazetidine‐A; 6‐[5‐(azetidin‐2‐ylmethoxy)pyridin‐3‐yl]hex‐5‐yn‐1‐ol) and some sulfur‐bearing analogues were tested for their activities in vitro against human α4β2‐, α4β4‐, α3β4*‐ and α1*‐nicotinic acetylcholine receptors (nAChRs). AMOP‐H‐OH was also assessed in an antidepressant efficacy model. AMOP‐H‐OH and some of its analogues have high potency and selectivity for α4β2‐nAChRs over other nAChR subtypes. Effects are manifested as partial agonism, perhaps reflecting selectivity for high sensitivity (α4)₃(β2)₂‐nAChRs. More prolonged exposure to AMOP‐H‐OH and its analogues produces inhibition of subsequent responses to acute challenges with full nicotinic agonists, again selectively for α4β2‐nAChRs over other nAChR subtypes. The inhibition is mediated either via antagonism or desensitization of nAChR function, but the degree of inhibition of α4β2‐nAChRs is limited by the partial agonist activity of the drugs. Certain aspects of the in vitro pharmacology suggest that AMOP‐H‐OH and some of its analogues have a set of binding sites on α4β2‐nAChRs that are distinct from those for full agonists. The in vitro pharmacological profile suggests that peripheral side effects of AMOP‐H‐OH or its analogues would be minimal and that their behavioral effects would be dominated by central nAChR actions. AMOP‐H‐OH also has profound and high potency antidepressant‐like effects in the forced swim test. The net action of prolonged exposure to AMOP‐H‐OH or its analogues, as for nicotine, seems to be a selective decrease in α4β2‐nAChR function. Inactivation of nAChRs may be a common neurochemical endpoint for nicotine dependence, its treatment, and some of its manifestations, including relief from depression.