A Forgotten Chiral Spiro Compound Revisited: 3,3'‐Dimethyl‐3H,3'H‐2,2'‐spirobi[[1,3]benzothiazole]

The title compound was obtained as a side product during dimerization‐oxidation steps of the carbene generated from N‐methylbenzothiazolium iodide. Chromatography on (S,S)‐Whelk O1 column showed on cooling a typical plateau shape chromatogram indicating an exchange between two enantiomers on the column. The thermal barrier to racemization was determined (85 kJ.mol^?1 at 10 °C) by dynamic high‐performance liquid chromatography (DHPLC).The absolute configuration of the first (M) and second eluted (P) enantiomers on the (S, S)‐Whelk O1 column was established by comparing the reconstructed circular dichroism (CD) spectra from the CD detector signal and the calculated CD spectrum of the (P) enantiomer. Mass spectrometry revealed that 3,3'‐dimethyl‐3H,3'H‐2,2'‐spirobi[[1,3]benzothiazole] can be viewed as a masked thiophenate attached to a benzothiazolium framework. Chirality 27:716–721, 2015. © 2015 Wiley Periodicals, Inc.     

Determination of absolute configuration in 4‐aryl‐3,4‐dihydro‐2(1H)‐pyrimidones by high performance liquid chromatography and CD spectroscopy

The absolute configuration of three 4‐aryl‐3,4‐dihydro‐2(1H)‐pyrimidones (Biginelli compounds, DHPMs) was established by comparison of the typical circular dichroism (CD) spectra of individual enantiomers with reference samples of known absolute configuration. The enantiomers were obtained by semipreparative separation of racemic mixtures on a Chiralcel OD‐H chiral stationary phase. The method was used to establish the enantiopreference of various lipases in biocatalytic kinetic resolution experiments employing activated DHPM esters. Chirality 11:659–662, 1999. © 1999 Wiley‐Liss, Inc.     

Resolution of 1‐n‐Butyl‐3‐Methyl‐3‐Phospholene 1‐Oxide With TADDOL Derivatives and Calcium Salts of O,O'‐Dibenzoyl‐(2R,3R)‐ or O,O'‐di‐p‐Toluoyl‐(2R,3R)‐tartaric Acid

The resolution methods applying (?)‐(4R,5R)‐4,5‐bis(diphenylhydroxymethyl)‐2,2‐dimethyldioxolane (“TADDOL”), (?)‐(2R,3R)‐α,α,α',α'‐tetraphenyl‐1,4‐dioxaspiro[4.5]decan‐2,3‐dimethanol (“spiro‐TADDOL”), as well as the acidic and neutral Ca²⁺ salts of (?)‐O,O'‐dibenzoyl‐ and (?)‐O,O'‐di‐p‐toluoyl‐(2R,3R)‐tartaric acid were extended for the preparation of 1‐n‐butyl‐3‐methyl‐3‐phospholene 1‐oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single‐crystal X‐ray analysis. The absolute P‐configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. Chirality 26:174–182, 2014. © 2014 Wiley Periodicals, Inc.     

Synthesis and optical resolution of 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole‐2‐carboxylic acid

Site selective mono‐ and dimetalation methods have been developed for the functionalization of 1‐[(1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole. Optical resolution of the prepared 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]pyrrole‐2‐carboxylic acid provided new atropisomeric 1‐arylpyrrole derivatives. The absolute configuration of the pure dicarboxylic acid enantiomers was determined by single crystal X‐ray diffraction and CD spectroscopy. Chirality 2009. © 2009 Wiley‐Liss, Inc.     

Application of (S)‐TBMB carboxylic acid‐based on‐line HPLC‐exciton CD analysis to acyclic vicinal alcohols and amino alcohols

Applications of the on‐line HPLC‐exciton CD analysis using (S)‐2‐tert‐butyl‐2‐methyl‐1,3‐benzodioxole‐4‐carboxylic acid [(S)‐TBMBC‐OH] that can simultaneously determine the enantiomeric compositions and the absolute configuration of cyclohexane‐1,2‐diols and diamines as well as acyclic vicinal diols and amino alcohols were studied. Di‐O‐ or di‐N,O‐(S)‐TBMBC derivatives of acyclic terminal vicinal diols, 2‐hydroxy‐1‐amines, and nonterminal vicinal diols gave symmetrical exciton CD spectra between enantiomers, indicating their absolute configurations. However, Di‐N,O‐(S)‐TBMBC derivatives of 2‐amino‐1‐ols did not always give symmetrical exciton CD spectra between enantiomers, but their 2‐phthalimido‐1‐O‐(S)‐TBMBC derivatives gave symmetrical exciton CD spectra, indicating their absolute configurations. All these (S)‐TBMBC derivatives were separated by normal‐phase HPLC and unequivocally determined by the on‐line HPLC‐exciton CD analysis without recourse to reference samples. Chirality 11:149–159, 1999. © 1999 Wiley‐Liss, Inc.     

Absolute Configurations of Four Resorcylic Acid Lactones,Paecilomycins J − M,by CD/TDDFT Calculations

The absolute configurations of four resorcylic acid lactones (RALs), paecilomycins J ? M ( 1 ? 3 and 5 ), were assigned by Time‐Dependent Density‐Functional Theory (TDDFT) calculations of their electronic circular dichroism (CD) spectra. The previously reported structure 4 for paecilomycin M was found to be incorrect and should be changed to structure 5 . Analysis of structure‐spectrum relationship for this group of RALs suggested that V′‐shape conformations give type I CD spectra (two negative Cotton effects around 300 and 260 nm, a positive Cotton effect around 220 nm) while V‐shape conformations yield type II spectra (signs of three Cotton effects were opposite to those in type I). Chirality 26:44–50, 2013. © 2013 Wiley Periodicals, Inc.     

Synthesis and characterization of high quantum yield and oscillator strength 6‐chloro‐2‐(4‐cynophenyl)‐4‐phenyl quinoline (cl‐CN‐DPQ) organic phosphor for solid‐state lighting

A novel blue luminescent 6‐chloro‐2‐(4‐cynophenyl) substituted diphenyl quinoline (Cl‐CN DPQ) organic phosphor has been synthesized by the acid‐catalyzed Friedlander reaction and then characterized to confirm structural, optical and thermal properties. Structural properties of Cl‐CN‐DPQ were analyzed by Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) spectroscopy, X‐ray diffraction technique (XRD) and scanning electron microscopy (SEM) and energy dispersive analysis of X‐ray (EDAX) spectroscopy. FTIR spectra confirmed the presence of different functional groups and bond stretching. ¹H–NMR and ¹³C–NMR confirmed the formation of an organic Cl‐CN‐DPQ compound. X‐ray diffraction study provided its crystalline nature. The surface morphology of Cl‐CN‐DPQ was analyzed by SEM, while EDAX spectroscopy revealed the elemental analysis. Differential thermal analysis (TGA/DTA) disclosed its thermal stability up to 250°C. The optical properties of Cl‐CN‐DPQ were investigated by UV–vis absorption and photoluminescence (PL) measurements. Cl‐CN‐DPQ exhibits intense blue emission at 434 nm in a solid‐state crystalline powder with CIE co‐ordinates (0.157, 0.027), when excited at 373 nm. Cl‐CN‐DPQ shows remarkable Stokes shift in the range 14800–5100 cm^?1, which is the characteristic feature of intense light emission. A narrow full width at half‐maximum (FWHM) value of PL spectra in the range 42–48 nm was observed. Oscillator strength, energy band gap, quantum yield, and fluorescence energy yield were also examined using UV–vis absorption and photoluminescence spectra. These results prove its applications towards developing organic luminescence devices and displays, organic phosphor‐based solar cells and displays, organic lasers, chemical sensors and many more.     

Host–guest inclusion complex of mesalazine and β‐cyclodextrin and spectrofluorometric determination of mesalazine

The supramolecular interaction of mesalazine (MSZ) and β‐cyclodextrin (β‐CD) has been examined by ultraviolet–visible (UV–vis) light, infra‐red (IR) light and fluorescence spectroscopy. The formation of an inclusion complex has been confirmed based on the changes of the spectral properties. MSZ–β‐CD host–guest complex was formed in (1:1) stoichiometry and the inclusion constant (K = 1.359 × 10² L mol^–1) was ascertained by typical double reciprocal plots. Furthermore, the thermodynamic parameters (ΔG°, ΔH° and ΔS°) of (MSZ–β‐CD) were obtained. Based on the remarkable enhancement of the fluorescence intensity of MSZ produced through complex formation, a simple, accurate, rapid and highly sensitive spectrofluorometric method for the determination of MSZ in aqueous solution in the presence of β‐CD was developed. The measurement of relative fluorescence intensity was carried with excitation at 330 nm and emission 493 nm. All variables affecting the reactions were studied and optimized. Beer's law was obeyed in the concentration range 0.1–0.45 µg/mL. Absorbance was found to increase linearly with increasing concentration of MSZ, which is corroborated by the calculated correlation coefficient values of 0.99989. The molar absorptivity, Sandell's sensitivity, detection and quantification limits were calculated. The validity of the described methods was assessed, and the method was successfully applied to the determination of MSZ in its pharmaceutical formulation. In addition, a solid inclusion complex was synthesized by co‐precipitation method. Copyright © 2014 John Wiley & Sons, Ltd.     

Stopped‐Flow Enantioselective HPLC‐CD Analysis and TD‐DFT Stereochemical Characterization of Methyl Trans‐3‐(3,4‐Dimethoxyphenyl)Glycidate

Caffeic acid‐derived polyethers are a class of natural products isolated from the root extracts of comfrey and bugloss, which are endowed with intriguing pharmacological properties as anticancer agents. The synthesis of new polyether derivatives is achieved through ring‐opening polymerization of chiral 2,3‐disubstituted oxiranes, whose absolute configurations define the overall stereochemistry of the produced polymer. The absolute stereochemistry of one of these building blocks, methyl trans‐3‐(3,4‐dimethoxy‐phenyl)glycidate ( 3 ), was therefore characterized by the combination of enantioselective high‐performance liquid chromatography (HPLC), electronic circular dichroism (ECD) spectroscopy, and time‐dependent density functional theory (TD‐DFT) calculations. Initial efforts aiming at the isolation of enantiomers by means of a standard preparative HPLC protocol followed by offline ECD analysis failed due to unexpected degradation of the samples after collection. The stopped‐flow HPLC‐CD approach, by which the ECD spectra of enantiomers are measured online with the HPLC system, was applied to overcome this issue and allowed a fast, reliable, and chemical‐saving analysis, while avoiding the risks of sample degradation during the collection and processing of enantiomeric fractions. Subsequent TD‐DFT calculations identified ( (2S,3R)-3 as the first eluted enantiomeric fraction on the Lux Cellulose‐2 column, therefore achieving a full stereochemical characterization of the chiral oxirane under investigation. Chirality 27:914–918, 2015. © 2015 Wiley Periodicals, Inc.     

Asymmetric catalysis of homo‐coupling of 3‐substituted naphthylamine and hetero‐coupling with 3‐substituted naphthol leading to 3,3′‐dimethyl‐2,2′‐diaminobinaphthyl and ‐2‐amino‐2′‐hydroxybinaphthyl

Optically active 3,3′‐dimethyl‐2,2′‐diamino‐1,1′‐binaphthyl (DM‐DABN) and 3,3′‐dimethyl‐2‐amino‐2′‐hydroxybinaphthyl (DM‐NOBIN) derivatives were synthesized by Cu‐(?)‐sparteine complex‐catalyzed enantioselective homo‐ and hetero‐coupling of 2‐naphthylamine, respectively. The difference in enantioselectivity was observed by changing the concentration of oxygen. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Selective recognition of thymidine homopolymer (poly T) oligonucleotide with cobalt(II)–4‐[(5‐chloro‐2‐pyridyl)azo]‐1,3‐diaminobenzene complex

The interactions of cobalt(II)–4‐[(5‐chloro‐2‐pyridyl)azo]‐1,3‐diaminobenzene (5‐Cl‐PADAB) complex with different kinds of homopolymer oligonucleotides in basic medium were investigated based on the measurements of resonance light scattering, UV–vis, circular dichroism spectra and dark field light‐scattering imaging. Experiments showed that only thymidine homopolymer (poly T) oligonucleotides with the length in the range of poly T₆ to poly T₁₈ could interact with the Co(II)–5‐Cl‐PADAB complex in alkaline conditions and cause evident color and spectral change. Thus, the binary complex of Co(II)–5‐Cl‐PADAB could be employed as a visual probe for selectively recognizing the poly T oligonucleotides. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis,HPLC Enantioresolution,and X‐ray Analysis of a New Series of C5‐methyl Pyridazines as N‐Formyl Peptide Receptor (FPR) Agonists

The synthesis of three racemates and the corresponding non‐chiral analogues of a C5‐methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC‐UV were investigated using four chiral stationary phases (CSPs: Lux Amylose‐2, Lux Cellulose‐1, Lux Cellulose‐2 and Lux Cellulose‐3). The best resolution was achieved using amylose tris(5‐chloro‐2‐methylphenylcarbamate) (Lux Amylose‐2), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X‐ray crystallographic analysis and comparative chiral HPLC‐UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC₅₀ values in the micromolar range. Chirality 25:400–408, 2013. © 2013 Wiley Periodicals, Inc.     

Discrimination of Axial and Central Stereogenic Elements in Chiral Bis(oxazolines) Based on Atropisomeric 3,3′‐Bithiophene Scaffolds Through Chiroptical Spectroscopies

Two diastereoisomeric pairs of bis‐oxazolines, provided with a stereogenic center at carbon 4 and based on the 3,3′‐bithiophene atropisomeric scaffold, were synthesized and structurally characterized. They differ in the substituents at positions 2 and 5 of the thiophene rings, which are functionalized with methyl (1) or phenyl (2) groups, respectively. In vibrational circular dichroism (VCD) spectra, recorded in CCl₄ solutions, it is possible to distinctly recognize the characteristic features of axial and central stereogenic elements. In tandem with Density Functional Theory (DFT) calculations, the absolute configuration (AC) of the diastereoisomers was safely established. In this case, VCD was shown to be superior to ECD (electronic circular dichroism) in the assignment of AC. The normal modes, evaluated from DFT calculations, show that the VCD signals in correspondence with the stereogenic axis of the bithiophene unit are different for 1 and 2. The VCD spectra of a molecular analog of 1, the (S)‐2,2′,5,5′‐tetramethyl‐4,4′‐bis‐(diphenylphosphino)‐3,3′‐bithiophene oxide (3), characterized by the same 3,3′‐bithiophene scaffold, but devoid of stereogenic centers, exhibits signals similar to those observed in the case of diastereoisomer (aS,R,R)‐1a, associated with almost identical normal modes. Chirality 28:686–695, 2016. © 2016 Wiley Periodicals, Inc.     

Preparative Enantioseparation of β‐Substituted‐2‐Phenylpropionic Acids by Countercurrent Chromatography With Substituted β‐Cyclodextrin as Chiral Selectors

Preparative enantioseparation of four β‐substituted‐2‐phenylpropionic acids was performed by countercurrent chromatography with substituted β‐cyclodextrin as chiral selectors. The two‐phase solvent system was composed of n‐hexane‐ethyl acetate‐0.10 mol L‐1 of phosphate buffer solution at pH 2.67 containing 0.10 mol L^‐1 of hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) or sulfobutylether‐β‐cyclodextrin (SBE‐β‐CD). The influence factors, including the type of substituted β‐cyclodextrin, composition of organic phase, concentration of chiral selector, pH value of the aqueous phase, and equilibrium temperature were optimized by enantioselective liquid–liquid extraction. Under the optimum separation conditions, 100 mg of 2‐phenylbutyric acid, 100 mg of tropic acid, and 50 mg of 2,3‐diphenylpropionic acid were successfully enantioseparated by high‐speed countercurrent chromatography, and the recovery of the (±)‐enantiomers was in the range of 90–91% for (±)‐2‐phenylbutyric acid, 91–92% for (±)‐tropic acid, 85–87% for (±)‐2,3‐diphenylpropionic acid with purity of over 97%, 96%, and 98%, respectively. The formation of 1:1 stoichiometric inclusion complex of β‐substituted‐2‐phenylpropionic acids with HP‐β‐CD was determined by UV spectrophotometry and the inclusion constants were calculated by a modified Benesi‐Hildebrand equation. The results showed that different enantioselectivities among different racemates were mainly caused by different enantiorecognition between each enantiomer and HP‐β‐CD, while it might be partially caused by different inclusion capacity between racemic solutes and HP‐β‐CD. Chirality 27:795–801, 2015. © 2015 Wiley Periodicals, Inc.     

Geometric enantiomerism in cyclic compounds: Chiral dibrominated 1,3‐dioxanes

The first geometric enantiomers in the cyclic compounds series are reported. The investigated compounds are 2,2‐disubstituted‐5‐methyl‐1,3‐dioxane derivatives in which the substituents at position 2 bear chiral centers with identical substituents but with opposite configurations. The structure of the unlike isomers was determined from the solid state molecular structure of the compounds obtained by single crystal X‐ray diffractometry and the enantiomers of these diastereoisomers were observed by chiral column HPLC base‐line separation. The investigated compounds were obtained by a diastereoselective bromination reaction of the corresponding 2,2‐dialkyl and 2,2‐dibenzyl‐5‐methyl‐1,3‐dioxanes. Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

Chiral overcrowded alkenes; asymmetric synthesis of (3S,3'S)-(M, M)-(E)-(+)-1,1',2,2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4, 4'-biphenanthrylidenes

An asymmetric synthesis route towards (3S,3'S)-(M,M)-(E)-(+)-1,1',2, 2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4,4'-biphenanthrylidene was developed using the Evans procedure as a key step. The absolute configurations of the title compound and of its parent ketone were determined by CD spectroscopy and could be correlated with the stereochemical results of the asymmetric alkylation. Furthermore, a comparison was made with the known (3R,3'R)-(P,P)-(E)-(-)-1,1',2,2', 3,3',4,4'-octahydro-3,3',7,7'-dimethyl-4,4'-biphenanthrylidene. Finally, the X-ray crystallographic analysis of (3S,3'S)-(M, M)-(E)-(+)-1,1',2,2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4, 4'-biphenanthrylidene is presented.     

Chromogenic and fluorescent ‘turn‐on’ chemodosimeter for fluoride based on a F–‐triggered cascade reaction

We developed a new chromogenic and fluorescent ‘turn‐on’ chemodosimeter 1 based on a F^–‐triggered cascade reaction. This system displayed significant changes in UV/vis absorption and fluorescence emission intensities selectively for F^– over other anions in a mixture of CH₃CN/H₂O (95 : 5, v/v) and in acetonitrile. Copyright © 2014 John Wiley & Sons, Ltd.     

Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine]

It was shown that racemic (±)‐ 2 [1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine], WMS‐1813 ] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ₁ receptors. To study the pharmacological activity of the enantiomers of 2 , a preparative HPLC separation of (R)‐2 and (S)‐2 was performed. The absolute configuration of the enantiomers was determined by CD‐spectroscopy together with theoretical calculations of the CD‐spectrum of a model compound. In receptor binding studies with the radioligand [³H]‐(+)‐pentazocine, (S)‐2 was thrice more potent than its (R)‐configured enantiomer (R)‐2 . The metabolic degradation of the more potent (S)‐enantiomer was considerably slower than the metabolism of (R)‐2 . The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap‐LC‐MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2 . Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

Investigation on the analytical application of cationic Gemini surfactant 12‐4‐12 and its interaction with DNA

The quantitative determination of nucleic acids is of great importance in fundamental research and clinical diagnosis. In this work, the interaction between DNA and cationic Gemini surfactant 12‐4‐12, which changes the conformation of DNA, was investigated by UV‐vis absorption, FT‐IR spectra and steady‐state fluorescence techniques. A hydrophobic pyrene probe was used to investigate the microenvironment change and calculate the critical micelle concentration (CMC) of Gemini surfactant 12‐4‐12 (0.69 mmol/L), which is close to the value obtained from the conductivity method (0.79 mmol/L). A new detection assay for DNA is proposed with Gemini surfactant 12‐4‐12, using the resonance light‐scattering (RLS) technique. The formation of DNA–12‐4‐12 complex resulted in enhanced RLS signals at 368 nm, which is proportional to DNA concentration in the range 0.304–5.32 mg/L, with a detection limit of 35 µg/L. Most coexisting substances do not interfere in the detection and four synthetic samples were analyzed satisfactorily. Copyright © 2011 John Wiley & Sons, Ltd.     

Properties,theoretical study and crystal structure of 3‐benzothiazole‐9‐ethyl carbazole

The title compound of 3‐benzothiazole‐9‐ethyl carbazole was synthesized by the reaction of 3‐aldehyde‐9‐ethyl carbazole and 2‐aminothiophenol. The compound was characterized by ¹H nuclear magnetic resonance (NMR) and mass spectrometry (MS). Its crystal structure was obtained and determined by single crystal X‐ray diffraction. The results showed that the crystal belongs to the orthorhombic crystal system and the cell parameters of space group P2(1)2(1)2(1) were a = 5.6626 (12) Å, b = 12.606 (3) Å, c = 22.639 (5) Å, α = 90°, β = 90°, γ = 90°, V = 1616.0 (6) ų, Z = 4, Dc = 1.350 mg/m³. The UV–vis and fluorescence spectra were also studied preliminarily. The fluorescence spectra of the title compound with bovine serum albumin (BSA) showed that BSA could be marked with the compound and the stability constant between them was 0.82 × 10⁷ M^?1. Meanwhile, the crystal and molecule were theoretically surveyed by density functional tight‐binding (DFTB). The results showed that there was an orbital overlap for lowest unoccupied molecular orbital (LUMO) between the neighbouring molecules for the crystal, which is different from the molecule structure. It was also showed that the crystal structure is a non‐conductor. Copyright © 2016 John Wiley & Sons, Ltd.