Synthesis of naproxen via regioselective ring opening of (2S,3S)-epoxy-1-butanol

(S)-Naproxen was synthesized by the regioselective and stereospecific epoxide ring opening of (2S,3S)-epoxy-1-butanol (2) with diethyl-2-(6-methoxynaphthyl)aluminium (5) as the key step. Thus, treatment of di-ethylaluminate of 2 with 5 at 0° afforded (2S,3S)-3-(6-methoxy-2-naphthyl)butan-1,2-diol (6) , which was oxidized by sequential treatment with sodium periodate and potassium permanganate in a mixture of tert-butyl-alcohol and phosphate buffer (pH 7.0) to give naproxen in high enantiomeric purity.     

Enantiomeric separation of oxybutynin by recycling high‐speed counter‐current chromatography with hydroxypropyl‐β‐cyclodextrin as chiral selector

Recycling high‐speed counter‐current chromatography was successfully applied to the preparative separation of oxybutynin enantiomers. The two‐phase solvent system consisted of n‐hexane, methyl tert‐butyl ether, and 0.1 mol/L phosphate buffer solution (pH = 5.0) with the volume ratio of 6:4:10. Hydroxypropyl‐β‐cyclodextrin was employed as the chiral selector. The influence of factors on the chiral separation process, including the concentration of chiral selector, the equilibrium temperature, the pH value of the aqueous phase were investigated. Under optimum separation conditions, 15 mg of oxybutynin racemate was separated with the purities of both the enantiomers over 96.5% determined by high‐performance liquid chromatography. Recovery for the target compounds reached 80–82% yielding 6.00 mg of (R)‐oxybutynin and 6.15 mg of (S)‐oxybutynin. Technical details for recycling elution mode were discussed.     

Butyllithium Addition to α‐Chiral Compounds: Solvent Mixture Effects on Diastereofacial Selectivity

Temperature‐dependent selectivity in nucleophilic additions is affected by the solvent. In this context, we investigated the effect on diastereoselectivity of solvent mixtures with respect to pure solvents. Binary systems of THF/hexane and of four different hydrocarbon mixtures were employed in BuLi addition to 2‐phenylpropanal, (2S)‐2‐[(tert‐butyl)dimethylsilyloxy]‐2‐phenylethanal, and (2S)‐2‐[(tert‐butyl)dimethylsilyloxy]‐N‐(trimethylsilyl)propan‐1‐imine. A 5‐mol‐% of THF in hexane affects the isomer ratio by reducing both ΔΔH^≠ and ΔΔS^≠ contributions, and suppresses T_inv. On the contrary, in hydrocarbon binary mixtures, the T_inv is still observed and occurs at a higher temperature than in pure solvents. Studying the dependence of T_inv on the hexane/decane mixture composition, we propose the formation of a peculiar solvation cluster that is unaffected by the composition of the bulk reaction solvent.     

Stereoselective separation of (1S, 4S)‐sertraline from medicinal reaction mixtures by countercurrent chromatography with hydroxypropyl‐β‐cyclodextrin as stereoselective selector

Four stereoisomeric components were produced during the synthesis of the antidepressant drug (1S, 4S)‐sertraline hydrochloride due to the two chiral carbon centers in its chemical structure, including (1S, 4S), (1R, 4R), (1S, 4R), and (1R, 4S)‐isomer. Stereoselective separation of the target isomer (1S, 4S)‐sertraline from the medicinal reaction mixtures by countercurrent chromatography using hydroxypropyl‐β‐cyclodextrin as the stereoselective selector was investigated. A biphasic solvent system composed of n‐hexane/0.20 mol/L phosphate buffer solution with pH 7.6 containing 0.10 mol/L of hydroxypropyl‐β‐cyclodextrin (1:1, v/v) was selected for separation of cis‐sertraline and trans‐sertraline using reverse phase elution mode and (1S, 4S)‐sertraline was separated with (1R, 4R)‐sertraline using recycling elution mode. A fabricated in‐house analytical countercurrent chromatographic apparatus was used for optimization of the separation conditions. Stationary phase retention and peak resolution were investigated for separation of cis‐sertraline and trans‐sertraline by the analytical apparatus.     

Electroanalytical Studies on Cobalt(II) Ion‐Selective Sensor of Polymeric Membrane Electrode and Coated Graphite Electrode Based on N2O2 Salen Ligands

Poly(vinyl chloride)‐based membranes of salen ligands, 2‐((E)‐((1R,2S)‐2‐((E)‐5‐tert‐butyl‐2‐hydroxybenzylideneamino)cyclohexylimino)methyl)‐4‐tert‐butyl phenol (S₁) and 2‐((E)‐((1R,2S)‐2‐((E)‐3,5‐di‐tert‐butyl‐2‐hydroxybenzylideneamino)cyclohexylimino)methyl)‐4,6‐di‐tert‐butylphenol (S₂) were fabricated and explored as cobalt(II) selective electrodes. The performance of the polymeric membrane electrode (PME) and coated graphite electrode (CGE) were compared and it was observed that CGE showed a wide working concentration range of 1.1×10^?8 to 1.0×10^?1 mol L^?1 with a limit of detection of 7.0×10^?9 mol L^?1 exhibiting the Nernstian slope 29.6 mV/decade of activity in the pH range 3.0–9.0. It was used for the determination of cobalt(II) ions in water, soil, beer, pharmaceutical samples and medicinal plants and would be used as an indicator electrode in potentiometric titration with EDTA.     

Effect of Buffer Species on the Inclusion Complexation of Acidic Drug Celecoxib with Cyclodextrin in Solution

The interaction of celecoxib (Celox) with cyclodextrins (CDs) has been investigated by phase solubility techniques. In this study, the influences of CD type, pH, buffer type, buffer concentration and temperature on the tendency of Celox to form inclusion complexes with CDs were examined. The tendency of Celox to complex with CDs is in the order HP-β-CD > β-CD > γ-CD > α-CD, where the complex formation constants (K ₁₁) were 1377, 693, 126 and 60 M⁻¹, respectively. Also ionization of the slightly acidic Celox (pK _a=9.7) was found to reduce its tendency to complex (i.e., The K ₁₁ values of Celox/β-CD in 0.05 M phosphate buffer were 976 and 210 M⁻¹ for neutral and ionized Celox, respectively). Increasing citrate and phosphate buffer concentration enhances the tendency of ionized Celox to complex with β-CD as a result of a corresponding decrease in the inherent solubility (S ₀) of the Celox anion. On the other hand, these two buffers interact differently with neutral Celox and β-CD, where increasing phosphate buffer concentration at low pH enhances the complexation of neutral Celox by lowering S ₀, while increasing citrate buffer concentration at low pH reduces complex formation as citrate buffer species, mainly citric acid, act as a solublizer and a competitor for Celox and β-CD. The contribution of Celox hydrophobicity for complex stability constitutes about 77% of the driving force for complex stability. The complex formation of neutral Celox with β-CD (ΔG ⁰=−28.6 kJ/mol) is driven by both enthalpy (ΔH ⁰=−21.7 kJ/mol) and entropy (ΔS ⁰=23.3 J/mol K) changes.     

Preparative enantioseparation of propafenone by counter‐current chromatography using di‐n‐butyl l‐tartrate combined with boric acid as the chiral selector

This paper extends the research of the utilization of borate coordination complexes in chiral separation by counter‐current chromatography (CCC). Racemic propafenone was successfully enantioseparated by CCC with di‐n‐butyl l ‐tartrate combined with boric acid as the chiral selector. The two‐phase solvent system was composed of chloroform/ 0.05 mol/L acetate buffer pH 3.4 containing 0.10 mol/L boric acid (1:1, v/v), in which 0.10 mol/L di‐n‐butyl l ‐tartrate was added in the organic phase. The influence of factors in the enantioseparation of propafenone were investigated and optimized. A total of 92 mg of racemic propafenone was completely enantioseparated using high‐speed CCC in a single run, yielding 40–42 mg of (R)‐ and (S)‐propafenone enantiomers with an HPLC purity over 90–95%. The recovery for propafenone enantiomers from fractions of CCC was in the range of 85–90%.     

Enzymatic Synthesis of Nucleoside‐5′‐O‐(1‐thiophosphates) and (SP)‐Adenosine‐5′‐O‐(1‐thiotriphosphate)

Treatment of adenosine with PSCl₃ in trimethyl phosphate gave, after ion‐exchange chromatography, adenosine‐5′‐O‐monophosphate (AMP; 28%) and adenosine‐5′‐O‐monothiophosphate (AMPS; 48%). AMPS was studied as a thiophosphate residue donor in an enzymatic transphosphorylation with nucleoside phosphotransferase (NPase) of the whole cells of Erwinia herbicola. As exemplified by a number of natural and sugar‐ and base‐modified nucleosides, it was demonstrated that NPase of the whole cells of Erwinia herbicola catalyzes the transfer of both thiophosphate and phosphate residues with a similar efficiency. An incubation of AMPS in a phosphorylating extract of Saccharomyces cerevisiae (K‐phosphate buffer (0.3 M , pH 7.0); 3% glucose; 15 mM MgCl₂; 28°, 8 h), followed by ion‐exchange column chromatography afforded AMP (8%), AMPS (recovered, 23%), ATP (11%), and (S_P)‐adenosine‐5′‐O‐(1‐thiotriphosphate) ((S_P)‐ATPαS); (total yield 37%; 48% based on the consumed AMPS). For comparison of physicochemical properties, adenosine was chemically transformed into ATPαS as a mixture of the (S_P) (53%) and (R_P) (44%) diastereoisomers.     

Enzymatic oxidative polymerization of para‐imine functionalized phenol catalyzed by horseradish peroxidase

Enzymatic oxidative polymerization of a new para‐imine functionalized phenol derivative, 4‐(4‐hydroxybenzylideneamino)benzoic acid (HBBA), using horseradish peroxidase enzyme and hydrogen peroxide oxidizer has been investigated in an equivolume mixture of an organic solvent (acetone, methanol, ethanol, dimethylformamide, 1,4‐dioxane, and tetrahydrofuran) and phosphate buffer (pH = 5.0, 6.0, 6.8, 7.0, 7.2, 8.0, and 9.0) at different temperatures under air for 24 h. The resulting oligomer, oligo(4‐(4‐hydroxybenzylideneamino)benzoic acid) [oligo(HBBA)], was characterized using ultraviolet–visible, Fourier transform infrared (FT‐IR), ¹H nuclear magnetic resonance (NMR), cyclic voltammetry, size exclusion chromatography, differential scanning calorimetry, and thermogravimetric analyses. Polymerization involved carbon dioxide and hydrogen elimination from the monomer, and terminal units of the oligomer structure consisted of phenolic hydroxyl (–OH) groups at the ends. The polymer is mainly composed of a mixture of phenylene and oxyphenylene units according to ¹H NMR and FT‐IR analyses. Effects of solvent system, temperature and buffer pH on the polymerization have been investigated in respect to the yield and molecular weight (M_n) of the product. The best condition in terms of the highest molecular weight (M_n = 3000 g/mol, DP ~ 15) was achieved in an equivolume mixture of 1,4‐dioxane/pH 5.0 phosphate buffer condition at 35°C. Electrochemical characterization of oligo(HBBA) was investigated at different scan rates. The resulting oligomer has also shown relatively high thermal stability according to thermogravimetric analysis. Copyright © 2015 John Wiley & Sons, Ltd.     

Cobalt Phthalocyanine Molecular Electrode for the Electrochemical Investigation of the Release of Glutathione upon Copper‐Catalyzed Decomposition of S‐Nitrosoglutathione

Decomposition of S‐nitrosoglutathione (GSNO) in phosphate buffer solution at physiological pH 7.4 in the presence of cuprous ion as a catalyst and sodium borohydride as a reducing agent is analyzed by observing the transient apparition of reduced glutathione GSH through its electrooxidation. Transient formation of GSH, upon decomposition of 1 mM GSNO in presence of 0.025 mM Cu(NO₃)₂ and 1 mM NaBH₄ was detected by using an ordinary pyrolytic graphite electrode modified with an adsorbed monolayer of cobalt phthalocyanine at 0 V vs. SCE.     

Chromatographic Characterization of Molecularly Imprinted Microspheres Synthesized by Aqueous Microsuspension Polymerization：Influences of pH,Kinds and Concentration of Buffer on Capacity Factors

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Effects of solvents on the reactions of coordination complexes: Part 20. Kinetics and mechanism of base hydrolysis of (αβS) (Salicylato) (Tetraethylenepentamine) Cobalt(III) in aquo-organic solvent media

The kinetics of base hydrolysis of (αβS) (salicylato) (tetraethylenepentamine) cobalt(III) have been investigated in aquo-organic solvent media at 15.0 < t, °C < 40.0, and I = 0.10 mol dm (ClO₄^?) using propane-2-ol (?70% v/v), t-butanol (?60% v/v), acetone (?70% v/v), acetonitrile (?50% v/v), and ethylene glycol (?70% v/v) as cosolvents. Both the spontaneous and base-catalyzed hydrolysis of the phenoxide species [(tetren)CoO₂CC₆H₄O]⁺ were appreciably accelerated by the cosolvents PrⁱOH, Bu^tOH, Me₂CO, and MeCN. On the contrary the base hydroylsis (k₂) was retarded while spontaneous aquation (k₁) was accelerated to a small extent with increased EG content. Variation of log k₁ and log k (k = k₂ at I = 0) with mole fraction (_X0.S) or reciprocal of the relative permitivity (D_s^?1) of the media were nonlinear. The transfer free energy of the transition state relative to that of the initial state of the substrate for transfer of species from water to mixed solvents also varied nonlinearly with _X0.S, or D_s^?1 indicating solvent specificity. The activation parameters, ΔH^≠ and ΔS^≠ varied nonlinearly with solvent composition exhibiting extrema. The preferential solvation and solvent structural effects mediated the kinetics and energetics of the reaction. © 1995 John Wiley & Sons, Inc.     

Thermo‐ and pH‐induced phase transitions and network parameters of poly(N‐isopropylacrylamide‐ co‐2‐acrylamido‐2‐methyl‐propanosulfonic acid) hydrogels

Dual temperature‐ and pH‐sensitive hydrogels composed of N‐isopropylacrylamide (NIPAM) and 2‐acrylamido‐2‐methyl‐propanosulfonic acid (AMPS) were prepared by free‐radical crosslinking copolymerization in aqueous solution at 22 °C. The mole percent of AMPS in the comonomer feed was varied between 0.0 and 7.5, while the crosslinker ratio was fixed at 5.0/100. The effect of AMPS content on thermo‐ and pH‐ induced phase transitions as well as equilibrium swelling/deswelling, interior morphology and network structure was investigated. The volume phase transition temperature (VPT‐T) was determined by both swelling/deswelling measurements and differential scanning calorimetry (DSC) technique. In addition, the volume phase transition pH (VPT‐pH) was detected from the derivative of the curves of the swelling ratio (dQ_v/dpH) versus pH. The polymer‐solvent interaction parameter (χ) and the average molecular mass between crosslinks ( ) of hydrogels were calculated from swelling ratios in buffer solutions at various pHs. The enthalpy (ΔH) and entropy (ΔS) changes appearing in the χ parameter of hydrogels were also determined by using the modified Flory–Rehner equation. The negative values for ΔH and ΔS indicated that the hydrogels had a negative temperature‐sensitive property in water, that is, swelling at a lower temperature and shrinking at a higher temperature. It was observed that the experimental swelling data of hydrogels at different temperature agreed with the modified Flory‐Rehner approach based on the affine network model. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1713–1724, 2008     

Versatile Stereoselective Synthesis of Completely Protected Trifunctional α-Methylated α-Amino Acids Starting from Alanine

A new route to completely protected α-methylated α-amino acids starting from alanine is described (see Scheme). These derivatives, which are obtained via base-catalyzed opening of the oxazolidinones (2S,4R)- and (2R,4S)- 2 , can be directly employed in peptide synthesis. The synthesis of both enantiomers of Z-protected α-methylaspartic acid β-(tert-butyl)ester (O⁴-(tert-butyl) hydrogen 2-methylaspartates (R) or (S)- 4a ), α-methyl-glutamic acid γ-(tert-butyl) ester (O⁵-(tert-butyl) hydrogen 2-methylglutamate (R)- or (S)- 4b ), and of N^ε-bis-Boc-protected α-methyllysine (N⁶,N⁶-bis[(tert-butyloxy)carbonyl]-2-methyllysine (R)- or (S)- 4c ) is described in full detail.     

(μ‐Tri‐tert‐butoxysilanethiol­ato)­bis[(tetra­hydro­furan)lithium(I)] and catena‐poly[[bis­(μ‐tri‐tert‐butoxy­silanethiol­ato)dilithium(I)]‐μ‐dimethoxy­ethane]: solvent coordination as the structure‐forming factor

The title compounds, μ‐(tri‐tert‐butoxy­silanethiol­ato‐κ²S:S)‐bis[(tetra­hydro­furan‐κO)lithium(I)], [Li₂(C₁₂H₂₇O₃SSi)₂(C₄H₈O)₂], (I), and catena‐poly[[bis­(μ‐tri‐tert‐butoxysilanethiol­ato)‐1:2κ²S;1κS:2κS,O‐dilithium(I)]‐μ‐dimethoxy­ethane‐κ²O:O′], [Li₂(C₁₂H₂₇O₃SSi)₂(C₄H₁₀O₂)]_n, (II), were obtained by the reaction of tri‐tert‐butoxy­silanethiol with metallic lithium. The crude product, when recrystallized from tetra­hydro­furan (THF) yields (I), and when recrystallized from 1,2‐dimethoxy­ethane (DME) gives (II). Compound (I) forms centrosymmetric dimers in the solid state with an Li₂S₂ central core, whereas (II) forms infinitely long chains, in which the centrosymmetric dimeric units are linked together by the bidentate DME ligand (also residing on an inversion centre), thus forming a coordination polymer. The formation of a one‐dimensional structure in (II) is a consequence of replacement of a monodentate THF solvent mol­ecule with a bidentate DME mol­ecule.     

Enantioselective Catalysis CXLI [1]. Tridentate Ligands with 1-(Pyridin-2-yl)ethylamine as Chiral Building Block in the Enantioselective Transfer Hydrogenation of Acetophenone

Summary.  A series of novel tridentate ligands with nitrogen and oxygen donor sites was synthesized starting from enantiomerically pure (S)- and (R)-1-(pyridin-2-yl)ethylamine, the preparation and resolution of which was developed. The new optically active ligands were tested as in situ catalysts together with Ru(PPh₃)₃Cl₂ in the enantioselective transfer hydrogenation of acetophenone with isopropanol. The secondary amine ligand (S)-2,4-di-tert-butyl-6-(1-(pyridin-2-yl)ethylamino)methylphenol gave the best results with almost quantitative conversion and 47%ee. Received August 17, 2001. Accepted August 27, 2001     

Effects of organic solvents and ionic liquids on the aminolysis of (RS)-methyl mandelate catalyzed by lipases

The enzymatic resolution of (RS)-methyl mandelate with n-butylamine using lipases in organic solvents (n-hexane, tert-butanol, and chloroform) and ionic liquids [BMIm][BF₄] and [BMIm][PF₆] is reported. The amide configuration is dependent on the organic solvent. When using mixtures of chloroform or tert-butanol/ionic liquids (10:1 v/v) with CAL-B as the catalyst, the amides were obtained in high enantiomeric excess (ee_p >99% and E >200).     

Intermediates of Asymmetric Oxidation Processes Catalyzed by Vanadium(V) Complexes

The [VO(acac)₂]/Schiff base [R-2-(N-3,5-di-tert-butylsalicylidene)amino-2-phenyl-1-ethanol, S-2-(N-3,5-di-tert-butylsalicylidene)amino-3,3-dimethyl-1-butanol, S-2-(N-3,5-di-tert-butylsalicylidene)amino-3-methyl-1-butanol, or R-2-(N-3,5-di-tert-butylsalicylidene)amino-3-phenyl-1-propanol]/H₂O₂ catalytic systems for the asymmetric oxidation of sulfides and the [VO(acac)₂]/(3bR,4aR)-2-(3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanol/tert-butyl hydroperoxide/TBHP and VO(OAlkyl)₃/[2,2]paracyclophane-4-carboxylic acid N-(1,1-dimethylethyl)-N-hydroxamide/TBHP catalytic systems for the asymmetric epoxidation of allylic alcohols were studied using ¹³C, ⁵¹V, and ¹⁷O NMR spectroscopy. The key intermediates of these systems (peroxo and alkylperoxo complexes of vanadium(V)) were detected, their structures in solution were studied, and the reactivity was evaluated.     

A Monolithic Hybrid Cellulose‐2.5‐Acetate/Polymer Bioreactor for Biocatalysis under Continuous Liquid–Liquid Conditions Using a Supported Ionic Liquid Phase

Mesoporous monolithic hybrid cellulose‐2.5‐acetate (CA)/polymer supports were prepared under solvent‐induced phase separation conditions using cellulose‐2.5‐acetate microbeads 8–14 μm in diameter, 1,1,1‐tris(hydroxymethyl)propane and 4,4′‐methylenebis(phenylisocyanate) as monomers as well as THF and n‐heptane as porogenic solvents. 4‐(Dimethylamino)pyridine and dibutyltin dilaurate (DBTDL), respectively, were used as catalysts. Monolithic hybrid supports were used in transesterification reactions of vinyl butyrate with 1‐butanol under continuous, supported ionic liquid–liquid conditions with Candida antarctica lipase B (CALB) and octylmethylimidazolium tetrafluoroborate ([OMIM⁺][BF₄^?]) immobilized within the CA beads inside the polymeric monolithic framework and methyl tert‐butyl ether (MTBE) as the continuous phase. The new hybrid bioreactors were successfully used in dimensions up to 2×30 cm (V=94 mL). Under continuous biphasic liquid–liquid conditions a constant conversion up to 96 % was achieved over a period of 18 days, resulting in a productivity of 58 μmol mg^?1(CALB) min^?1. This translates into an unprecedented turnover number (TON) of 3.9×10⁷ within two weeks, which is much higher than the one obtained under standard biphasic conditions using [OMIM⁺][BF₄^?]/MTBE (TON=2.7×10⁶). The continuous liquid–liquid setup based on a hybrid reactor presented here is strongly believed to be applicable to many other enzyme‐catalyzed reactions.     

The absolute configuration of (2S,4S)‐ and (2R,4R)‐2‐tert‐butyl‐4‐methyl‐3‐(4‐tolyl­sulfon­yl)‐1,3‐oxazolidine‐4‐carbaldehyde

The title enanti­omorphic compounds, C₁₆H₂₃NO₄S, have been obtained in an enanti­omerically pure form by crystallization from a diastereomeric mixture either of (2S,4S)‐ and (2R,4S)‐ or of (2R,4R)‐ and (2S,4R)‐2‐tert‐butyl‐4‐methyl‐3‐(4‐tolyl­sulfon­yl)‐1,3‐oxazolidine‐4‐carbaldehyde. These mixtures were prepared by an aziridination rearrangement process starting with (S)‐ or (R)‐2‐tert‐butyl‐5‐methyl‐4H‐1,3‐dioxine. The crystal structures indicate an envelope conformation of the oxazolidine moiety for both compounds.