Use of a chiral surfactant for enantioselective reduction of a ketone

The influence of a chiral surfactant and a polymer-supported chiral additive on reduction of ketones using sodium borohydride will be described. Initial preparations involved methylation of (S)-leucinol to give (2S)-N , N-dimethyl-2-amino-4-methyl-1-pentanol (1) (67%). The chiral surfactant (2) was synthesized by reacting (1) with bromohexadecane (71%). The functionalized styrene for the polymer-supported chiral additive (5) was synthesized by reacting (1) with 4-vinylbenzyl chloride. Polymerization was carried out with 10% of the functionalized monomer (4), 5% cross-linking agent divinylbenzene, and 85% styrene with AIBN as the initiator. The activity of the chiral surfactant and polymeric additive were examined by using them as additives in a standard reduction of 2-pentanone with sodium borohydride to yield (R)- and (S)-2-pentanol (3) (20%). The resulting alcohol was analyzed by polarimetry (ee 9.5%) and also esterified with (2S)-methylbutyric acid prior to characterization by NMR. 13C NMR indicated an enantiomeric excess of 5.2% when the chiral surfactant was used, and 7% when the polymeric additive was used.     

Chiral microemulsion electrokinetic chromatography with two chiral components: Improved separations via synergies between a chiral surfactant and a chiral cosurfactant

In this study, the combination of two chiral components in a microemulsion formulation for the separation of enantiomers via microemulsion EKC (MEEKC) was successfully accomplished. Previous publications of chiral microemulsions have utilized only one chiral entity; the surfactant, cosurfactant, or oil was chiral. This is the first study, to date, of the effects of using two chiral species in a single pseudostationary phase (PSP). The chiral surfactant dodecoxycarbonylvaline (DDCV) was used in conjunction with the chiral cosurfactant S-2-hexanol. Ethyl acetate was incorporated as the oil core of the microemulsion and the buffer was 50 mM phosphate at a pH of 7. Additionally, a microemulsion prepared with racemic 2-hexanol was used for comparison to a previous DDCV microemulsion and as a baseline for the newly formulated dual chiral microemulsion. The efficiencies, resolutions, and enantioselectivities for the S-2-hexanol, racemic 2-hexanol, and original 1-butanol DDCV microemulsions are compared. The hexanol-based PSPs provide improved efficiencies and resolutions. To evaluate the combination of each DDCV enantiomer (R and S) with S-2-hexanol, changes in Gibb's free energy were calculated. A synergistic effect was found when two chiral components were combined to form a microemulsion.     

一种新型的含联二萘结构的手性聚芳醚酮的合成及表征

目前,对于外消旋体的拆分已经越来越引起人们的关注,在药物化学领域中尤为突出,原因是手性药物的两个对映体虽然在物理和化学性质上大多相同,但其在药效及药物动力学方面却表现出很大的差别,目前尚没有通用的手性固定相用于外消旋体的拆分,为了解决这一问题,以淀粉、纤维素以及其衍生物制备的手性固定相已被人们广泛使用。     

Creation of novel chiral cryptophanes by a self-assembling method utilizing a pyridyl-Pd(II) interaction

[structure: see text]. This Letter demonstrates the molecular design of novel self-assembled chiral cryptophanes. Mediated by square-planar Pd(II) complexes, racemic pyridyl cyclotriveratrylene derivative rac-2 self-assembles into mixtures of racemic chiral cryptophanes and meso cryptophanes (1), which interconvert with each other, and the rates are remarkably enhanced by the addition of a slight excess of rac-2. On the other hand, optically resolved P-2 or M-2 self-assembles into the chiral cryptophane as the only product.     

Antiferroelectric phase induced by a semi-fluoroalkane positioned at the chiral tail of a molecule

A novel fluorinated chiral liquid crystal material derived from a newly designed optically active semi-perfluorinated alkyl chain in the chiral group, (S)-1-(2,2,3,3,3-pentafluoropropyloxy)-2-propanol, and a non-fluorinated homologue derived from (S)-1-propyloxy-2-propanol, were prepared for comparison of their mesomorphic properties. The investigation of defect textures, switching behaviour and dielectric permmitivity showed that the introduction of a semi-perfluorinated alkyl chain into the chiral tail of the molecule induces formation of an antiferroelectric phase.     

Enantioselective Strecker-type reaction to sulfonylimines having a 2-pyridylsulfonyl group as a novel stereocontroller

A catalytic enantioselective Strecker-type reaction to N-(2-pyridylsulfonyl)imines in the presence of chiral bis(oxazoline)s afforded the products with a high enantioselectivity. A dynamically induced new chiral center on the sulfur by discriminative coordination of a chiral Lewis acid to one of the sulfonyl oxygens efficiently controlled the enantioselectivity.     

Optimization of a capillary electrophoresis method to determine the chiral purity of a drug

Capillary electrophoresis (CE) using hydroxypropyl-β-cyclodextrin (HP-β-CD) in the separation buffer was investigated to determine the overall chiral purity of a drug containing a single stereogenic center. The effects of primary factors —pH, buffer components, buffer concentration, cyclodextrin concentration and sample amount (concentration and injection volume) — on the resolution of the enantiomers were investigated. Secondary factors such as the HP-β -CD source, lot and degree of substitution that were expected to affect the robustness of the assay were investigated also. The linearity, quantitation limit for the trace enantiomer and the precision of the measurements were determined. This study shows that understanding and optimizing the assay conditions leads to a chiral CE separation that is comparable to that obtained by chiral HPLC. However, chiral CE separations achieved with buffer additives have the advantages of shorter run times, higher numbers of theoretical plates (greater resolution), smaller amounts of chiral additive (less cost) and greater ruggedness (separation virtually independent of column properties unlike HPLC).     

Simultaneous Chiral Separation Using a Combinatorial Molecular Imprinting Phase

Molecular imprinting is a technology by which specific recognition sites can be producedby using a template molecule in the polymerization procedure. In recent years,molecular imprinting has become an important approach for the preparation of chiralstationary phase with predetermined selectivity'-'. So far, the commonly atilizedfunctional monomers include methacrylic acid', acrylamide' and 4-vinylpyridine',combined functional monomers such as methacrylic acid 2-vinylpyridine'-' andacrylamide…     

Requirements for the formation of a chiral template

The chemisorptive enantioselectivity of propylene oxide is examined on Pd(111) surfaces templated by chiral 2-methylbutanoate and 2-aminobutanoate species. It has been found previously that chiral propylene oxide is chemisorbed enantiospecifically onto Pd(111) surfaces modified by either (R)- or (S)-2-butoxide. The enantiomeric excess (ee) varied with template coverage, reaching a maximum of approximately 31%. Templating the surface using 2-methylbutanoate, where the chiral center is identical to that in the 2-butoxide species, but is now anchored to the surface by a carboxylate rather than an alkoxide linkage, shows no enantiospecificity. The enantioselectivity is restored when the methyl group is replaced by an amine group, where a maximum ee value of approximately 27% is found. DFT calculations and infrared measurements suggest that the structures of the butyl group on the surface are similar for both 2-butoxide and 2-methylbutanoate species, implying that gross conformational changes are not responsible for differences in chemisorptive enantioselectivity. There is no clear correlation between the location of the chiral center and enantioselectivity, suggesting that differences in the template adsorption site are also not responsible for the lack of enantioselectivity. It is proposed that the 2-butyl group in 2-methylbutanoate species is less rigidly bonded to the surface than that in 2-butoxides, allowing the chiral center to rotate azimuthally. It is postulated that the role of the amino group in 2-aminobutanoate species is to anchor the chiral group to the surface to inhibit azimuthal rotation.     

Supramolecular assembly facilitating adsorbate-induced chiral electronic states in a metal surface

Through the application of optically active second-harmonic generation measurements (OA-SHG) we have demonstrated that the adsorption of amino acids cysteine (HSCH(2)CHNH(2)COOH) and penicillamine (HSC(CH3)(2)CHNH(2)COOH) from solution can induce chiral electronic states in an initially achiral polycrystalline Au film. The chiral induction is strongly dependent upon the pH of the deposition solution; adsorption of penicillamine and cysteine under acidic conditions (pH = 3) induces the same level of optical activity, whereas at pH = 11, the optical activity induced by cysteine is reduced by ca. 50% and penicillamine does not induce optical activity at all. The pH dependence indicates that the presence of interadsorbate hydrogen bonds, and consequently the supramolecular assembly of the adsorbates, facilitates the induction of chiral electronic states in the Au surface. This observation demonstrates that the symmetry properties of the extended structure of the self-assembled layer, and not the local adsorption geometry of the isolated adsorbed moiety, play the lead role in the induction of chiral metallic electronic states. The dependence of the chiral induction on COOH groups is identical to that observed in studies of optical activity in chiral thiol-protected nanoparticles, suggesting a common mechanism for the chiral perturbation in extended films and nanoparticles.     

Breaking symmetry: spontaneous resolution of a polyoxometalate

A chiral polyoxometalate [Hf(PW11O39)2]10- (1) has been prepared and structurally characterized. It crystallizes in the chiral space group P2(1)2(1)2, as a conglomerate of two enantiomerically pure crystals in the absence of any chiral source. The absolute configuration of 1 was determined from the Flack parameter by X-ray crystallography. The structure of 1 comprises two lacunary [PW11O39]7- units, each functioning as a tetra-dentate ligand sandwiching an 8-coordinate HfIV centre in a distorted square antiprismatic geometry. Optically active crystals of both enantiomers were spectroscopically distinguishable by means of solid state circular dichroism spectroscopy. This hafnium-substituted polyoxometalate (POM), 1, shows that spontaneous chiral resolution, a rare phenomenon, can be operable in POM systems.     

Chiral separation of polychlorinated biphenyls using a combination of hydroxypropyl-gamma-cyclodextrin and a polymeric chiral surfactant

Chiral separation of moderately to highly hydrophobic polychlorinated biphenyls (PCBs) using a conventional chiral micelle or a polymeric chiral surfactant, as the single chiral selector is very difficult since the hydrophobic interactions between the chiral PCB and the monomeric or polymeric surfactant is very strong. Combined use of a polymeric chiral surfactant, polysodium N-undecanoyl-D-valinate (poly-D-SUV) with hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) was successful in cyclodextrin modified electrokinetic chromatography (CD-EKC) enantioseparation of PCB congeners. Addition of HP-gamma-CD to the background electrolyte containing poly-D-SUV functioned to improved chiral resolution for the PCBs and reduce the analysis time for these congeners. In addition, concentration of methanol, concentration of 2-(N-cyclohexylamino) ethanesulfonic acid (CHES) buffer and separation voltage was also varied to optimize multicomponent separation of five chiral PCBs. Simultaneous separation and enantioseparation of all five PCBs was possible in less than 50 min under optimized conditions that requires a 5 mM CHES solution buffered at about pH 10 with 1.5% w/v (ca. 60 mM) poly-D-SUV and 16 mM HP-gamma-CD. In addition, 1 M urea and 20% v/v methanol should be added as organic modifier and the capillary temperature maintained at 45 degrees C. As expected the polymeric surfactant showed improved chiral resolution of PCBs over conventional micelles of SUV. Under optimized conditions, when CD-EKC of chiral PCBs using poly-D-SUV was compared to sodium dodecyl sulfate (SDS), better resolution, higher efficiency and shorter analysis time was achieved with poly-D-SUV.     

Exploring the spectral enantiodiscrimination potential of a DNA-based orienting medium using deuterium NMR spectroscopy

(2)H-{(1)H} 1D and 2D-NMR spectroscopy is used to evaluate the enantiodiscrimination potential of DNA-based, lyotropic chiral mesophases on a series of (pro)chiral amino acids.     

An optimised synthetic approach to a chiral derivatising agent and the utilisation of a dimerisation reaction in the synthesis of a novel C2-symmetric diphosphine ligand

We report an optimised synthetic approach to the chiral derivatising agent (5R)-methyl-1-(chloromethyl)-2-pyrrolidinone. In addition, the observation of an unwanted dimerisation product is turned to our advantage by providing a method for the synthesis of a new class of C2-symmetric chiral diphosphine.     

Electron capture dissociation distinguishes a single D-amino acid in a protein and probes the tertiary structure

First results are reported on the application of ECD in analysis of 2+ and 3+ ions of stereoisomers of Trp-cage (NLYIQWLKDGGPSSGRPPPS), the smallest and fastest-folding protein, which exhibits a tightly folded tertiary structure in solution. The chiral recognition based on the ratios of the abundances of z(18) and z(19) fragments in ECD of 2+ ions was excellent even for a single amino acid (Tyr) D-substitution (R(chiral) = 8.6). The chiral effect decreased with an increase of temperature at the electrospray ion source, as well as at a higher degree of ionization, 3+ ions (R(chiral) = 1.5). A general approach is suggested for charge localization in n+ ions by analysis of ECD mass spectra of (n + 1)+ ions. Application of this approach to 3+ Trp-cage ions revealed the protonation probability order in 2+ ions: Arg(16) > Gln(5) > approximately N-terminus. The ECD results for native form of the 2+ ions favor the preservation of the solution-phase tertiary structure, and chiral recognition through the interaction between the charges and the neutral bond network. Conversely, ECD of 3+ ions supports the dominance of ionic hydrogen bonding which determines a different gas-phase structure than found in solution. Vibrational activation of 2+ ions indicated greater stability of the native form, but the fragmentation patterns did not provide stereoisomer differentiation, thus underlying the special position of ECD among other MS/MS fragmentation techniques. Further ECD studies should yield more structural information as well as quantitative single-amino acid D/L content measurements in proteins.     

De novo synthesis of Tamiflu via a catalytic asymmetric ring-opening of meso-aziridines with TMSN3

An asymmetric ring-opening reaction of meso-aziridines with TMSN3 was developed using a catalyst prepared from Y(OiPr)3 and chiral ligand 2 in a 1:2 ratio. Excellent enantioselectivity was realized from a wide range of substrates with a practical catalyst loading. The products were efficiently converted to enantiomerically enriched 1,2-diamines, which are versatile chiral building blocks for pharmaceuticals and chiral ligands. This reaction was applied to a catalytic asymmetric synthesis of Tamiflu, a very important anti-influenza drug containing a chiral 1,2-diamino functionality.     

Spontaneous chiral resolution of a coordination polymer with distorted helical structure consisting of achiral building blocks

Reaction of achiral 2,5-diphenyl-3,4-di(3-pyridyl)cyclopenta-2,4-dien-1-one (2) with ZnCl2 and HgBr2, respectively, afforded the helically chiral coordination polymers [(2)ZnCl2]infinity and [(2)HgBr2]infinity, which show spontaneous chiral resolution, forming colonies of homochiral crystals.     

Catalytic asymmetric cyclopropanation at a chiral platform

Novel chiral Robson-type macrocyclic complexes M(2)-L [where M = Mn(II), Mn(III), Co(II) and Co(III) and L denotes tetra-Schiff base chiral ligands, L1 or L2] have been synthesized by metal template condensation of 2,6-diformyl-4-methyl-phenol, with 1R,2R-diaminocyclohexane (L1) or 1R,2R-diphenylethylenediamine (L2). The dinuclear Co(II) and Co(III) complexes catalyze asymmetric cyclopropanation of styrene with diazoacetate cooperatively and with high enantioselectivity.     

Tripodal borate ligands from tris(dimethylamino)borane: the first synthesis of a chiral tris(methimazolyl)borate ligand, and the crystal structure of a single diastereomer pseudo-C3-symmetric Ru(II) complex

The activation of tris(dimethylamino)borane towards reaction with a chiral methimazole by N-methylimidazole has been used to prepare the first example of a chiral tris(methimazolyl)borate ligand. Coordination of this neutral ligand to Ru(II) has been achieved by reaction with [(p-cymene)RuCl(2)](2) to provide a single diastereomer complex in which the chirality of the methimazolyl substituents dictate the chirality of the bicyclo[3.3.3]cage formed by the ligand on coordination to the metal. The alternative approach to chiral tris(methimazolyl)borate ligands involving the introduction of a chiral group onto the boron atom has been explored by replacing N-methylimidazole in the above reaction by chiral oxazolines as activating bases in reaction with simple methimazole. However, although the B(NMe(2))(3) is activated to reaction with methimazole by these oxazolines, an intramolecular oxazoline ring-opening by a coordinated methimazolyl sulfur occurs and prevents the successful synthesis of these ligands.     

Enantioselective photooxidation of a sulfide by a chiral ruthenium(II) complex immobilized on a montmorillonite clay surface: the role of weak interactions in asymmetric induction

The present work pursued a possibility that enantioselectivity was achieved through weak intermolecular interactions between a catalyst and a substrate. For that purpose, we studied the photooxidation of alpha-ethylbenzyl phenyl sulfide catalyzed by a polypyridyl ruthenium(II) complex as a chiral photosensitizer. No covalent bonding was formed between a catalyst and a substrate, because the complexes used ([Ru(phen)(3)](2+) or [Ru(bpy(3))(2+)]) were coordinatively saturated. Enantiomer excess (ee) was attained to be 30% when a chiral photosensitizer was immobilized on montmorillonite clay. It was even improved to 43% in the presence of an additional chiral auxiliary, dibenzoyl-D(+)-tartaric acid. Notably, no enantioselectivity was achieved when the reaction took place in homogeneous solutions. The ab initio calculations were performed on the stability of an associate composed of a catalyst (metal complex) and a product (sulfoxide) to obtain a clue to reaction mechanisms. The calculations suggest that chiral discrimination is achieved even through noncovalent interactions between a substrate and a chiral sensitizer when the attacking direction by a substrate toward a catalyst is limited sterically on a solid surface.