Mizoroki-Heck Cyclizations of Amide Derivatives for the Introduction of Quaternary Centers.

We report non-decarbonylative Mizoroki-Heck reactions of amide derivatives. The transformation relies on the use of nickel catalysis and proceeds using sterically hindered tri- and tetrasubstituted olefins to give products containing quaternary centers. The resulting polycyclic or spirocyclic products can be obtained in good yields. Moreover, a diastereoselective variant of this method gives access to an adduct bearing vicinal, highly substituted sp3 stereocenters. These results demonstrate that amide derivatives can be used as building blocks for the assembly of complex scaffolds.

Formation of Cyclopenta[c]pyridine Derivatives from 2,5-Disubstituted Pyrroles and 1,4-Dibromo-1,3-butadienes via Pyrrole-Ring One-Carbon Expansion.

Reactions between 1,4-dibromo-1,3-butadienes and 2,5-disubstituted pyrroles afforded cyclopenta[c]pyridine derivatives in high yield, catalyzed by palladium and a cyclopentadiene-phosphine ligand (L1). Insertion of one terminal carbon of the butadienyl skeleton into one C═C double bond in the pyrrole ring resulted in ring expansion, along with a 1,2-shift of an alkyl or an aryl substituent on the butadienes.

Evaluation of synergistic enantioseparation systems with chiral spirocyclic ionic liquids as additives by capillary electrophoresis.

In recent years, chiral ionic liquids (CILs) have attracted more and more attention in the field of enantioseparation. In this study, two novel spirocyclic chiral ionic liquids, 1-butyl-3-methylimidazolium(T-4)-bis[(2S)-2-(hydroxy-κO)-3-methylbutanoato-κO]borate (BMIm(+)BLHvB(-)) and 1-butyl-3-methylimidazolium (T-4)-bis[(αS)-α-(hydroxy-κO)-4-methylbenzeneacetato-κO]borate (BMIm(+)BSMB(-)), were applied for the first time in capillary electrophoresis (CE) to establish synergistic systems for enantiomeric separation. Significantly improved separations of five tested analytes were observed in the CILs synergistic systems based on three ß-cyclodextrin derivatives (CD), compared with conventional single CD separation systems. Several principal parameters such as CILs concentration, cyclodextrin concentration, buffer pH, and applied voltage were systematically investigated with BMIm(+)BLHvB(-)/hydroxypropyl-ß-CD selected as a model system to optimize the enantioseparation. Molecular modeling was applied to further demonstrate the chiral recognition mechanism of the CILs/hydroxypropyl-ß-CD synergistic system, which showed a good agreement with the experimental results.

Establishment and Evaluation of the Novel Tetramethylammonium-L-Hydroxyproline Chiral Ionic Liquid Synergistic System Based on Clindamycin Phosphate for Enantioseparation by Capillary Electrophoresis.

Much attention has been paid to chiral ionic liquids (ILs) in analytical chemistry, especially its application in capillary electrophoresis (CE) enantioseparation. However, the investigation of chiral ionic liquids synergistic systems based on antibiotic chiral selectors has been reported in only one article. In this work, a novel chiral ionic liquid, tetramethylammonium-L-hydroxyproline (TMA-L-Hyp), was applied for the first time in CE chiral separation to evaluate its potential synergistic effect with clindamycin phosphate (CP) as the chiral selector. As observed, significantly improved separation was obtained in this TMA-L-Hyp/CP synergistic system compared to TMA-L-Hyp or a CP single system. Several primary factors that might influence the separation were investigated, including CP concentration, TMA-L-Hyp concentration, buffer pH, types and concentrations of organic modifier, applied voltage, and capillary temperature. The best results were obtained with a 40 mM borax buffer (pH 7.6) containing 30 mM TMA-L-Hyp, 80 mM CP, and 20% (v/v) methanol, while the applied voltage and temperature were set at 20 kV and 20°C, respectively.

Study on clarithromycin lactobionate based dual selector systems for the enantioseparation of basic drugs in capillary electrophoresis.

In this paper, the use of clarithromycin lactobionate, a kind of antibiotic chiral selector, in combination with four neutral cyclodextrin derivatives (glucose-ß-cyclodextrin, hydroxyethyl-ß-cyclodextrin, methyl-ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) was reported for the first time. As a result, these dual systems gave much better resolution of nefopam (the Rs increased to 3.58, 2.72, 1.49 and 1.42, respectively) compared to the single systems. The effects of buffer pH and selector concentration on the separation of nefopam were also investigated. Additionally, some other basic drugs including metoprolol, atenolol, propranolol, bisoprolol, esmolol and ritodrine were tested for the investigation and evaluation of the enantiorecognition capability of the four dual systems. As expected, the synergistic effect was observed in four systems. Different results of these dual systems were also summarized.

Tetramethylammonium-lactobionate: A novel ionic liquid chiral selector based on saccharides in capillary electrophoresis.

Chiral ionic liquids (ILs) have aroused widespread interest in separation science; however, only a few papers have reported the application of chiral ILs in CE for enantioseparation, and the use of chiral ILs as the sole chiral selector in an electrophoretic or a chromatographic system was reported in only three papers. In this study, we designed a lactobionic acid LA-based IL, tetramethylammonium-lactobionate (TMA-LA), and it is very interesting to find that the chiral separation capability can be remarkably improved when a conventional saccharide chiral selector evolved into an IL chiral selector. A comparative study of the enantiorecognition capability of three separation systems (single LA system, LA + TMA-chloride (TMA-Cl) system, and TMA-LA IL system) was also conducted, and the results showed that the use of TMA-LA IL as the sole chiral selector exhibited a remarkable superiority. A series of parameters affecting the enantioseparation, such as the type and proportion of organic modifier, buffer composition and pH, chiral selector concentration, as well as applied voltage were systematically investigated. The best enantioseparation was obtained at pH 7.6 using a 40 mM borax buffer with 40% v/v methanol, 200 mM TMA-LA, and 20 kV applied voltage. It is the first time that a saccharide-based IL is evaluated as a sole chiral selector in CE, and we hope this study would provide a new direction for the development of novel ILs chiral selectors based on conventional chiral selectors.

Study of the enantioseparation capability of chiral dual system based on chondroitin sulfate C in CE.

It has been reported that chiral dual system is able to improve the enantioseparation of enantiomers in many cases. Currently, the dual systems involved in CE chiral separation are mostly dual CDs systems, and the polysaccharides-based chiral dual system was reported in only one paper. To the best of our knowledge, the use of chondroitin sulfate C (CSC)-based dual system for enantiomeric separation has not been reported previously. Herein, four CSC-based chiral dual systems, namely CSC/glycogen, CSC/chondroitin sulfate A (CSA), CSC/hydroxypropyl-ß-CD (HP-ß-CD), as well as CSC/ß-CD (ß-CD), were evaluated for the first time for their enantioseparation capability by CE in this paper. During the course of the work, the influences of chiral selector concentration and buffer pH values on enantioseparation in dual systems were systematically investigated. Under the optimized conditions, the dual system consisting of CSC and glycogen exhibited better separations toward nefopam, duloxetine, sulconazole, atenolol, laudanosine, and cetirizine enantiomers compared to the single CSC or glycogen system. The combination of CSC and HP-ß-CD improved the separation of amlodipine and chlorphenamine enantiomers. However, no synergistic effect was observed in the CSC/CSA and CSC/ß-CD systems.

Investigation of the enantioselectivity of tetramethylammonium L-hydroxyproline ionic liquid as a novel chiral ligand in ligand-exchange CE and ligand-exchange MEKC.

Chiral ionic liquids (ILs) have drawn more and more attention in separation science; however, only a few papers focused on the application of chiral ILs as chiral ligands in LE-CE. In this article, a novel amino acid ionic liquid (AAIL), tetramethylammonium L-hydroxyproline ([TMA][L-OH-Pro]), was first applied as a chiral ligand to evaluate its enantioselectivity towards several aromatic amino acids in ligand-exchange capillary electrophoresis (LE-CE) and ligand-exchange micellar electrokinetic capillary chromatography (LE-MEKC). In the LE-CE system, excellent separations were achieved for tryptophan (Rs = 3.03) and 3, 4-dihydroxyphenylalanine (DOPA) (Rs = 4.35). Several parameters affecting the enantioseparation were systematically investigated, including AAIL concentration, type and concentration of central metal ion, buffer pH, as well as applied voltage. The optimum separation was obtained with 60 mM AAIL containing 30 mM Cu (II) at pH 4.5. Additionally, an LE-MEKC system was established to further study the enantioselectivity of [TMA][L-OH-Pro] towards selected analytes. As observed, the separations of the enantiomers of tryptophan, phenylalanine, and histidine were all improved compared to the LE-CE system. The results indicated that the application of AAILs as chiral ligands is a promising method in chiral separation science.

Evaluation of ionic liquids-coated carbon nanotubes modified chiral separation system with chondroitin sulfate E as chiral selector in capillary electrophoresis.

Nanoparticles (NPs) and ionic liquids (ILs) have been extensively studied and have aroused considerable interest in separation science; however, the employment of ILs-dispersed NPs as buffer modifiers for CE chiral separation has not been previously studied. In this work, we describe a new CE method using ILs dispersed multi-walled carbon nanotubes (ILs-MWNTs) as a modifier for enantioseparation with a polysaccharide, chondroitin sulfate E (CSE), as the chiral selector. As observed, significantly improved separations, including better enantioselectivity and improved peak shapes, were obtained in the ILs-MWNTs modified separation system for all drug enantiomers compared to the single CSE system. Several parameters affecting the enantioseparation, such as the choice of ILs and carbon nanoparticles, ILs-MWNTs concentration, chiral selector concentration, buffer pH and applied voltage, were systematically investigated. Satisfactory separations were achieved when 2.4µg/mL ILs-MWNTs were introduced into the 20mM Tris/H3PO4 buffer solution containing 2.5% CSE at pH 2.8-3.4 with a 15kV applied voltage. A brief mechanism of the enhanced enantioseparation capability of the ILs-MWNTs modified chiral separation system was also discussed.