Some new protocols for the assignment of absolute configuration by NMR spectroscopy using chiral solvating agents and CDAs

The utility of enantiopure BINOL (1,10-Bi-2-naphthol), in a ternary ion-pair complex, which is obtained using a carboxylic acid and an organic base, as a versatile chiral solvating agent (CSA) has been demonstrated for chiral analysis and the absolute configuration assignment of hydroxy acids. Another protocol where the utility of NOBIN as a CSA has been developed for discrimination and absolute configuration assignment of acids, hydroxy acids and their derivatives with a distinct strategy where a third ingredient, p-toluenesulfonic acid (p-TsOH) serves as a linker. In addition some three component chiral derivatization protocols have been introduced, such as the use of 2-formylphenylboronic acid and enantiopure mandelic acid or a primary amine for the determination of the configuration of primary amines and hydroxy acids, respectively. A simple, rapid and highly efficient three component chiral derivatizing protocol has also been discussed which was developed for assigning the absolute configuration of chiral α-hydroxy acids and their derivatives, which involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and (S)-[1,1-binaphthalene]-2,2-diamine separately. In a few examples, the DFT based theoretical calculations have been carried out to determine the geometry optimized structures of the complexes.     

Immobilization of Lecitase® ultra on recyclable polymer support: application in resolution of trans-methyl (4-methoxyphenyl)glycidate in organic solvents

Lecitase® Ultra was immobilized on epoxy-activated polymer (DILBEAD-VWR) functionalized with polyethyleneimine via adsorption and crosslinking with glutaraldehyde. The resolution of methyl trans-(±)-3-(4-methoxyphenyl) glycidate was carried out in xylene (e.e. >99%, conversion 50%). The enzyme is not inhibited by the 4-methoxy phenyl acetaldehyde produced during hydrolysis and the immobilized enzyme with 7% moisture content works efficiently in an organic phase. While the immobilized enzyme can be recycled several times, the polymer support can also be recycled after removing the immobilized enzyme by washing with 1?M HCl.     

An efficient synthesis of the opioid analgesic (R)-phenampromide via an aziridinium ion

A simple and efficient synthesis of the opioid analgesic agent (R)-phenampromide with high enantiopurity (>99% ee) via the formation of an aziridinium ion as a key step using commercially available starting material is described.     

A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-d-arabinitol using Co(III)(salen)-catalyzed hydrolytic kinetic resolution of a two-stereocentered anti-azido epoxide

A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-d-arabinitol, (+)-DAB-1, has been described in good overall yield (18.1%) and with high enantiomeric purity (up to 98% ee) starting from a simple raw material, cis-2-butene-1,4-diol. The Co-catalyzed hydrolytic kinetic resolution of a two-stereocentered racemic azido epoxide followed by asymmetric dihydroxylation of the alkene and ‘one pot’ reductive cyclisation of the azido diol are key reactions in the synthetic sequence.     

Resolution,absolute configuration and antifilarial activity of coumarinyl amino alcohols

The resolution of racemic coumarinyl amino alcohols 5–10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-l-proline (S)-11. Direct esterification of rac-5–10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5–10 and (R)-(?)-5–10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(?)-9 and (S)-(+)-10, (R)-(?)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action.     

Chiral benzimidazoles and their applications in stereodiscrimination processes

Chiral aspects of benzimidazoles have been over-shadowed for a long time due to the large number of reports on benzimidazoles in the medical field in numerous categories of therapeutic agents. The vigorous research activity in chiral applications of benzimidazole derivatives started after bifunctional benzimidazoles made their appearance especially in the last 2–3 decades. Thus, chiral benzimidazoles form a comparatively young branch of chiral chemistry. The presence of pyridine and pyrrole type of nitrogens along with the fused benzene ring confer on this class of molecules, special properties including useful nucleophilicity, hydrogen bonding ability and a rigid backbone, all of which play decisive roles in proven chiral applications. The present review aims to cover the synthetic routes to access chiral benzimidazoles and their applications in a plethora of chiral fields including enantioselective organocatalysis, metal-based catalysis, asymmetric transformations involving benzimidazole-N-heterocyclic carbenes, kinetic resolution, benzimidazole-based macrocyclic hosts in chiral supramolecular chemistry and other miscellaneous chiral applications.     

Synthesis of chiral carbosilane dendrimers with l-cysteine and N-acetyl-l-cysteine on their surface and their application as chiral selectors for enantiomer separation by capillary electrophoresis

The synthesis of chiral carbosilane dendrimers functionalized with cysteine and N-acetylcysteine groups is presented. These dendrimers were obtained through thiol–ene addition reactions and their application as chiral selectors in capillary electrophoresis was investigated. Four drugs used as model compounds were analyzed under different experimental conditions observing that the use of a first generation dendrimer containing 4 terminal N-acetyl-l-cysteine groups enabled the enantiomeric discrimination of razoxane with a discrimination power similar to that obtained with other powerful chiral selectors such as cyclodextrins.     

Benzyl isobornyl amines: a simple and practical class of NMR discriminating agents for effective chiral recognition of acids

The design and synthesis of a few simple N-benzyl derivatives of isobornyl amine is presented. The derivatives have been assessed as chiral solvating agents for effective discrimination of the signals of some acids in NMR analysis. The single crystal X-ray analysis of the salts of (R)-mandelic acid with two of the title derivatives help to understand the supramolecular interactions and assign the induced chemical shifts in ¹H NMR analysis. The title derivative is found to be suitable for quantitative determination of the enantiomeric excess of unknown enantiomeric purity as well as being efficient in resolving racemic mandelic acid.     

Design,synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

A series of novel N-1 and C-3 substituted indole derivatives (5a–f) were designed, synthesized and evaluated for their cytotoxic properties, viz Brine Shrimp Lethality Bioassay (BSLB) besides 5-Lipoxygenase (5-LOX) inhibitory activities through in vitro assays. Structure Activity Relation (SAR) studies showed that compound 5d with an LC₅₀ of 6.49 μM and 5c with an IC₅₀ of 33.69 μM were found to be interesting for cytotoxicity and 5-LOX inhibitory activity respectively.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

Adsorption of Basic Magenta II onto H2SO4 activated immature Gossypium hirsutum seeds: Kinetics,isotherms, mass transfer,thermodynamics and process design

The adsorption of Basic Magenta II onto H₂SO₄ activated immature Gossypium hirsutum seeds was analysed using Ho, modified Freundlich, Sobkowsk–Czerwi, Blanchard, Elovich, Avrami, and modified Ritchie kinetic models by nonlinear regression-sum of normalized errors analysis. The goodness of fit was evaluated with coefficient of determination and root mean square error. The good agreement of experimental data to Avrami second-order model indicated that the mechanism of adsorption followed multiple kinetic orders. The Avrami second-order mechanism was applied to predict the rate constant of sorption and the equilibrium capacity and subsequently the obtained equilibrium adsorption capacities were utilized to find the equilibrium concentrations. Langmuir, Freundlich, Temkin, Sips and Hill isotherms were investigated to understand the nature of adsorption with the help of nonlinear regression analysis. Both Sips and Hill isotherms were best fit to the adsorption equilibrium data showing the homogeneous adsorption on the heterogeneous surface of carbon and the positive co-operative manifestations of the Basic Magenta II molecules. The mass transfer study depicted the details such as mass transfer coefficient, intra-particle diffusion rate, pore diffusion coefficient, and film diffusion coefficient. The adsorption process was found to be controlled by film diffusion. The thermodynamic parameters like, Gibbs free energy change, enthalpy change, entropy change and isosteric heat of adsorption confirmed the endothermic, feasible and spontaneous nature of adsorption. A single stage batch adsorber was designed using Sips isotherm constants to estimate the amount of carbon required for desired purification.     

Amino acids as catalysts for the enolisation study of m-Methylacetophenone

Amino acids have been used as catalysts for the study of kinetic of enolisation of m-Methylacetophenone, in which iodination has been the chosen method. Several parameters like effect of ketone concentration, effect of dielectric constant, effect of catalysts etc. have been investigated for their effect on enolisation kinetics. The study is focused on β-alanine, dl-alanine, l-alanine and Glycine for their effects on the rate. The order of the rate constants obtained has been found to be in the order of increasing dipole moments of the amino acids i.e. l-alanine < Glycine < dl-alanine < β-alanine. With an increase in the temperature from 323 K to 338 K, an increase in the rate was from 1.3 to 2.12 mol^?1 min^?1. The ongoing reaction was found to be bimolecular in nature. The values of different thermodynamic parameters like Entropy (ΔS^≠), Enthalpy (ΔH^≠), Energy of activation (ΔEa) and Gibbs free energy (ΔF^≠) were found to be 6.20 e.u., 24.74 cal mol^?1, 25.20 k cal mol^?1 and 24.54 cal mol^?1 respectively.     

O-(α-Phenylethyl)hydroxylamine as a ‘chiral ammonia equivalent’: synthesis and resolution of 5-oxopyrrolidine- and 6-oxopiperidine-3-carboxylic acids

An approach to the synthesis and resolution of five- and six-membered lactams (i.e., 5-oxopyrrolidine- and 6-oxopiperidine-3-carboxylic acids) is described. The method relies on the one-pot Michael reaction—cyclization of itaconic acid or diethyl homoitaconate and enantiopure O-(α-phenylethyl)hydroxylamine as a ‘chiral ammonia equivalent’. It is shown that this chiral auxiliary can be used for the separation of diastereomeric lactam products and then easily removed by catalytic hydrogenolysis.     

A versatile ternary ion pair complex of 2′-amino-1,1′-binaphthalen-2-ol for sensing enantiomers and assignment of absolute configuration

2′-Amino-1,1′-binaphthalen-2-ol (NOBIN) serves as a versatile chiral solvating agent (CSA) in the presence of trifluoromethanesulfonic acid (TFMS). The formation of a ternary complex has been established by NMR, UV–Vis, fluorescence and IR studies. The mechanism of interactions among the three components in the ternary complex has been proposed and the ternary complex structures of different diastereomers have been established by DFT based theoretical calculations. The present protocol has its ubiquity not only in the analysis of the enantiomeric composition of molecules possessing diverse functionalities, but also in determining the stereospecific assignment of hydroxy acids.     

Molecular modelling,synthesis, and antimalarial potentials of curcumin analogues containing heterocyclic ring

The molecular modelling approach was applied to a series of nineteen curcumin analogues to find the possible PfRIO2 kinase inhibitory action. A putative active site in flexible loop (S1) of PfRIO2 kinase was explored computationally to recognize the molecular basis of ligands binding. The ligands (curcumin analogues; 3a–3s) were well accommodated in the selected active site (S1) due to their higher molecular size and length. Further all these synthesized compounds (3a–3s) were evaluated for their in vitro antimalarial activity according to the reported method. The antimalarial data showed that all these compounds to have parasiticidal activity with minimum killing concentrations (MKCs) range between 3.87 and 25.35 μM and schizonticidal activity with IC₅₀ range between 1.48 and 23.09 μM. The compound 3p showed the most significant result with maximum schizonticidal (IC₅₀; 1.48 ± 0.10 μM) and parasiticidal activities (MKC; 3.87 ± 0.36 μM) could be identified as promising lead for further investigations.     

Design,synthesis and antifungal evaluation of novel benzimidazole tertiary amine type of fluconazole analogues

A novel series of compounds containing tertiary amine moiety, substituted benzimidazole and triazole ring, initial design by molecular docking study of this scaffold at the active site of the fungal enzymes lanosterol 14α-demethylase (homology modeled of C. albicans) was synthesized by microwave irradiation and characterized by Proton Nuclear Magnetic Resonance (¹H NMR), Infra Red (IR), and Mass Spectroscopy (MS), and by elemental analysis. The screening of compound for in vitro (turbidimetric method) and in vivo (kidney burden test) antifungal activity against C. albicans revealed activity in many of the compounds as comparable to that of fluconazole.     

Synthesis of gold nanoparticles using herbal Acorus calamus rhizome extract and coating on cotton fabric for antibacterial and UV blocking applications

Gold nanoparticles (AuNPs) have been synthesized by greener method using chloroauric acid as precursor and extract of Acorus calamus rhizome as reducing agent. Formation of AuNP was confirmed by the presence of Surface Plasmon Resonance (SPR) peak in UV–Visible spectral analysis. XRD and FT-IR spectral analyses were performed for characterization. SEM images show spherical morphology and HR-TEM images reveal nanosize of AuNPs. The AuNPs were then coated on cotton fabric by pad-dry-cure method and characterized by SEM with EDAX technique. The results reveal the deposition of AuNPs on the surface of cotton fabric. Uncoated cotton, neat extract coated cotton and extract containing AuNPs coated cotton fabrics were then tested for antibacterial activity against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli) bacterial strains by AATCC 100 test method. It showed that the extract containing AuNPs coated cotton fabric had higher antibacterial activity than other test samples against E. coli. UV-DRS analysis performed on extract containing AuNPs coated cotton fabric showed improved UV-blocking property than uncoated cotton fabric and neat extract coated cotton fabric.     

Synthesis,characterization and antimicrobial studies on 13-membered-N6-macrocyclic transition metal complexes containing trimethoprim

Asymmetrical macrocyclic complexes of Mn^II, Co^II, Ni^II, Cu^II and Zn^II have been synthesized by the template process using bis(benzil)ethylenediamine as precursor. Bis(benzil)ethylenediamine reacts with transition metal chlorides and trimethoprim in a 1:1:1 molar ratio in methanol to give several solid metal complexes of the general composition [M(L)X₂] (M = Mn^II, Co^II, Ni^II, Cu^II and Zn^II, L = ligand and X = Cl^?). They were characterized by physicochemical and spectroscopic techniques. Based on analytical, spectral and magnetic moments, all the complexes are identified as distorted octahedral structures. All the complexes are of the [M(L)X₂] type. The shifts of the ν(CN) (azomethine) stretches have been monitored. To find out the donor sites of the ligands, the activity data show that the metal complexes are more potent than the parent ligand. The [M(L)X₂] complexes showed a broad spectrum of antimicrobial activity in vitro against both gram-positive and gram-negative human pathogenic bacterial isolates and the antimicrobial spectrum enhanced only with a combination of metal chlorides and trimethoprim complex. From the results it is imperative that the synthesized macrocyclic [M(L)X₂] complexes exhibit potent broad spectrum antibacterial activity.