Liquid Chromatographic Resolution of Enantiomeric Dipeptides on the Chiral Stationary Phase Derived from (S)-1-(6,7-Dimethyl-1-naphthyl)isobutylamine

Abstract

Liquid chromatographic resolution of fifteen enantiomeric dipeptide methyl esters as their N-3,5-dinitrobenzoyl derivatives was investigated on the chiral stationary phase (CSP) derived from (S)-1-(6,7-dimethyl-1-naphthyl)isobutylamine. The four stereoisomers present in each dipeptide derivative were observed to be separated quite well with the (R,R) isomer being eluted first. The separation factors for two enantiomeric pairs such as (R,R)/(S,S) and (R,S)/(S,R) and the elution orders are explained by two competing “opposite-sense” chiral recognition mechanisms.     

Normal Phase TLC Separation of Enantiomers Using Chiral Ion Interaction Agents

Abstract

A method for the thin layer chromatographic (TLC) separation of enantiomers and diastereomers involving the use of chiral ion interaction agents is described. Several aromatic amino alcohols were resolved by TLC on diol and/or high performance silica gel plates using a mobile phase containing (1R)-(-)- ammonium-10-camphorsulfonate or N-benzoxycarbonyl-glycyl-L-proline (ZGP). Many of these chiral aromatic amino alcohols are of pharmacological importance as α- and β-adrenergic blockers, adrenergic compounds, and anti-glaucoma agents. A comparison was made between various N-CBZ-amino acid derivatives as chiral counter ions/chiral mobile phase additives (CMAs). These separations could not be achieved on other normal phase TLC stationary phases including microcrystalline cellulose, alumina and ordinary silica gel plates.     

The influence of flexible spacer and the chirality of the core on the formation of chiral nematic phase of symmetric dimers containing trifluoromethyl terminal

Seven symmetric liquid crystal (LC) dimers containing different chiral cores and LC arms have been synthesised, termed EPDA-(R,S)PD, TFBDA-(R,S)PD, TFBA-(R,S)PD, TFBDA-(R)PD, TFBA-(R)PD, TFBDA-IB and TFBA-IB, respectively. TFBDA-(R,S)PD, TFBA-(R,S)PD, TFBDA-(R)PD and TFBDA-IB displayed chiral smectic A (SmA*) phase, while EPDA-(R,S)PD, TFBA-(R)PD and TFBA-IB exhibited chiral nematic (N*) phase. The effects of flexible spacer, structural type of LC arms and the chirality of the cores on the thermal properties of the dimers and the formation of N* phase have been studied. The results indicated that the chiral core was prone to induce the N* phase in LC dimer that contained nematic arms although the chirality of the core is very weak, while for the smectic LC arms containing CF3 terminal, the removal of the flexible spacer between chiral core and rigid LC units was conducive to the formation of N* phase. For example, TFBDA-(R)PD and TFBDA-IB displayed SmA* phase, while TFBA-(R)PD and TFBA-IB exhibited N* phase. However TFBA-(R,S)PD did not display N* phase, which reminded us that the chirality of the core and the conformation of the dimer also played an influence in the formation of the LC phase.     

(1S,2R)-N-(3,5-Dinitrobenzoyl) Norephedrine Bonded to Silica Gel as a Chiral Stationary Phase for the Liquid Chromatographic Separation of Enantiomers

Abstract

A Chiral Stationary Phase (CSP 3) was prepared by connecting (1S,2R)-N-(3,5-dinitrobenzoyl) norephedrine to a silica support through an ester linkage. CSP 3 was found to show some differences from CSP 1, derived from N-(3,5-dinitrobenzoyl) phenylglycine, in the resolution of N-acyl-1-aryl-1-aminoalkanes. For example, CSP 3 was found to show greater chiral recognition for conformationally rigid analytes than does CSP 1. On the other hand, CSP 1 was found to resolve flexible analytes better than CSP 3. To explain the chiral recognition behavior on CSP 3, the role of the conformational flexibility of CSP 3 in chiral recognition is proposed.     

Asymmetric Synthesis of Some Chiral Aryl and Hetero Aryl-Substituted β-, γ-, δ-Hydroxy Esters

Sixteen chiral β-, γ-, and δ-hydroxy esters with aryl, substituted aryl, and heteroaryl groups 2a–2s were synthesized by the asymmetric reduction of their corresponding keto esters 1a–1s as chiral pure reference compounds and starting materials. The asymmetric reduction was achieved by (R)-Me-CBS-oxazaborolidine. Ten new chiral γ- and δ-hydroxy esters 2d, 2e, and 2j–2s were obtained with high ee values and characterized by infrared, NMR (¹H and ¹³C), mass spectrometry, chiral high-performance liquid chromatography, and specific rotation.     

Synthesis of novel chiral compounds of purine and pyrimidine bases

The physiologically active groups such as purine and pyrimidine bases are introduced to the asymmetric ynthesis. The optically pure compounds bearing purine and pyrimidine bases (5a—5e) were prepared via the asymetric Michael addition reaction of purines and pyrimidines as Michael donators with the chiral source 5-(R)-[(1R, 2S, 5R)-menthyloxy]-2(5H)-furanone (3a), which was prepared from the natural chiral auxiliary (-)-menthol. The synthetic method was studied in detail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]_D~(20), IR, UV, ~1H NMR, ~(13)C NMR and MS. The absolute configuration of 5a was established by X-ray crystallography. The results provided an efficient synthetic route to chiral purines and pyrimidine analogues, and offered chiral sources for further research on the physiologically active compounds of chiral nucleotides.     

Direct Chiral Liquid Chromatographic Separation of Tocainide Enantiomers on a Crownpak (Cr) Column and its Application to Pharmaceutical Formulations and Biological Fluids

Abstract

Direct chiral liquid chromatographic resolution of racemic tocainide was accomplished without any derivatization using a crownpak CR(+) column as a chiral stationary phase. The stereochemical resolution (R) with symmetrical peaks was 0.97 and a separation factor (α) of 1.44 were obtained. Optimization of separation was achieved using different concentrations of perchloric acid.     

Direct Thin – Layer Chromatographic Separation of Enantiomers of Six selected Amino Acids Using 2-O-[(R)-2-Hydroxypropyl]-β-CD as a Mobile Phase Additive

Abstract

Compared with β-Cyclodextrin (β-CD), 2-O-[_(R)-2-hydroxypropyl]-β-CD (A) is more sensitive for chiral recognition. When (A) was used as the chiral mobile phase additive, some racemic amino acids were directly separated on silica gel TLC for the first time.     

Syntheses,characterizations, crystal structures,and in vitro antitumor activities of chiral triorganotin(IV) complexes containing (S)-(+)-2-(4-isobutyl-phenyl)propionic and (R)-(+)-2-(4-hydroxyphenoxy)propionic acid ligands

Four new chiral triorganotin(IV) carboxylates, [(R₃Sn)(O₂C₁₃H₁₇)] _n (R?=?Me 1, Ph 2), [(R₃Sn)(O₂C₁₃H₁₇)] (R?=?n-Bu 3), and [(R₃Sn)(O₄C₉H₉)] _n (R?=?Me 4), have been synthesized by reaction of (S)-(+)-2-(4-isobutyl-phenyl)propionic acid and (R)-(+)-2-(4hydroxyphenoxy)propionic acid with triorganotin(IV) chloride in the presence of sodium ethoxide. The complexes have been characterized by elemental analyses, FT-IR, NMR (¹H, ¹³C, and ¹¹⁹Sn) spectra, and X-ray crystallography diffraction analyses. Structural analyses show that 1 has a 1-D infinite chiral zigzag chain structure. Complexes 2 and 4 have a 1-D spring-like chiral helical chain with a channel, while 3 is a monomer. Antitumor activities of 1–4 have been studied.     

Facile Synthesis of (2R,3S)-2-Benzyloxy-3-hydroxybutyrolactone

The heterocyclic diols derived from L-dimethyl tartrate are important chiral synthons in organic synthesis. In particular, L-threosolactone and L-threosolactam structures are versatile precursors for the synthesis of biologically active molecules. Structurally, these functionalized five-membered rings contain two hydroxyl groups with R and S stereochemistry on C-2 and C-3 respectively. The preparation of (2R,3S)-2-benzyloxy-3-hydroxybutyrolactone (3) and of its derivatives, drawing upon L-dimethyl tartrate as an inexpensive chiral starting material, is described. The presented synthetic procedures are easy and effective for preparing L-threoso analogs. This protocol is also a better alternative in a large scale setup. All structures 3–6 and 8 are characterized using ¹H and ¹³C NMR spectroscopy.     

Synthesis and Characterization of Novel Chiral (1R,2R)-1,2-Bis[5-(Aminomethylphospinic Acid)-1,3,4-Thiadiazol-2-YL]Ethane-1,2-Diols

Abstract

(1R,2R)-1,2-bis[5-(arylideneamino)-1,3,4-thiadiazol-2-yl]ethane-1,2-diol (2a–d) were synthesized by using appropriate aldehydes and (1R,2R)-1,2-bis(5-amino-1,3,4-thiadiazol-2-yl)ethane-1,2-diol (1) as a starting compound. Then, the phosphinic acid component (3a–d) were obtained from (2a–d) and hypophosporus acid. In addition, the structures of the novel chiral compounds (2a–d) and (3a–d) were confirmed by elemental analyses, IR, ¹H-NMR, ¹³C-NMR, and ³¹P-NMR spectra.

¹H NMR and ¹³C NMR spectra for 1, 2a, and 3a (Figures S1–S6) are available online in the Supplemental Materials.     

Synthesis and Evaluation of a Synthetic Polymeric Chiral Stationary Phase for LC Based on the N, N′-[(1R,2R)-1,2-Diphenyl-1,2-Ethanediyl]bis-2-Propenamide Monomer

A synthetic polymeric chiral stationary phase for liquid chromatography based on N, N′-[(1R,2R)-1,2-diphenyl-1,2-ethanediyl]bis-2-propenamide monomer was prepared via a simple solution initiated radical polymerization. This stable chiral stationary phase showed enantioselectivities for a large number of racemates in polar organic and normal phase modes and high sample loading ability. However, none of the generated data has been optimized in terms of column performance. Different enantioselectivities were observed on this new chiral stationary phase compared with the commercial polymeric chiral stationary phase based on N-(2-acryloylamino-(1R,2R)-cyclohexyl)-acrylamine monomer. Consequently, these two chiral stationary phases are considered complementary to one another. Furthermore they utilize the same mobile phase and optimization procedures. This polymeric chiral stationary phase appears to be useful for preparative separations since high amounts of analyte can be injected without loosing enantioselectivity.     

HPLC Separation of the Diastereomeric Glutathione Adducts of Styrene Oxide

Abstract

The four diastereomeric thioether adducts resulting from the addition of glutathione to racemic styrene oxide were separated on a Radial Pak C₁₈ column using pH 7 Tris-phosphate buffer solution containing methanol as eluent. The benzylic thioether (1) eluted earlier than the benzylic alcohol (2) regioisomers. A complete stereochemical profile was established with the first eluting stereoisomer assigned as (S,R)-1, followed by (R,R)-1, (S,R)-2, and (R,R)-2,. The diastereomers with S configuration at the benzylic carbon emerged first for each set of regioisomers. The use of glutathione as a chiral probe for the analysis of enantiomerically enriched epoxides was illustrated with β-methylstyrene oxide formed from (1R, 2S)-N,N-dimethylephedrium bromide during the course of a chiral phase-transfer synthesis of oxiranes.     

Phase diagrams of cholesteric liquid crystals obtained with a generalized Landau-de Gennes theory

Abstract

Phase diagrams of chiral nematic liquid crystals are studied within the framework of a generalized Landau-Ginzburg-de Gennes theory. Using the parametrization of Grebel, Hornreich, and Shtrikman for the tensor order parameter Q, all relevant elastic terms are included for the helicoidal phase and the blue phases of chiral nematic liquid crystals up to fourth order in Q and its gradient ?Q. The influence of the additional elastic terms on the phase diagrams of the chiral nematic phases is then investigated. The theory correctly describes the variation of the pitch with temperature and the induced biaxiality of the cholesteric phase. The results resolve the discrepancies encountered by Hornreich and Shtrikman in the comparison of experiment and theory. New features in the topology of the phase diagrams of blue phases, like re-entrant phase transitions, are predicted.     

Synthesis of Novel Chiral Binaphthalene-Bridged Diporphyrins

Reactions of chiral 2,2′-biamino-1,1′-binaphthalene (R or S) with mono-substituted porphyrin 1a, 2b-c afforded novel chiral diporphyrins 3a-c and 4a-c which possess different linkers between the binaphthalene and porphyrin ring. Their structures have been identified by MS, IR, UV-visible and ¹H NMR spectra, and elemental analysis.     

Ferroelectric liquid crystal dopants with a chiral (R,R)‐2,3‐difluorooctyloxy side‐chain: host dependence of the polarization power

The polarization powers δ_p of four chiral dopants with (R,R)‐2,3‐difluorooctyloxy side‐chains were measured in four liquid crystal hosts with isotropic (I)–nematic (N)–smectic A (SmA)–smectic C (SmC) phase sequences. The four chiral dopants differ in terms of their core structures: 2‐phenylpyridine (MDW950), biphenyl (5), 2‐phenylpyrimidine (6) and 2‐(3‐nitrophenyl)pyrimidine (7). In each case, δ_p varies with the structure of the liquid crystal host, which is consistent with the behaviour of so‐called Type II dopants that normally feature a chiral core structure. The δ_p(host) profile was found to depend on the degree of biaxiality of the dopant core structure, and on the degree of steric coupling between the chiral 2,3‐difluorooctyloxy side‐chain and the core. Conformational analyses at the B3LYP/6‐31G* level suggest that the 2,3‐difluorooctyloxy side‐chain is conformationally more rigid than conventional chiral side‐chains due to the added electrostatic repulsion of the two adjacent fluoro groups combined with the hyperconjugative ‘gauche effect’, and may therefore have a higher degree of biaxiality on the time average. This biaxial character should make the chiral side‐chain more sensitive to variations in quadrupolar ordering imposed by the SmC phase of the liquid crystal host, and may therefore explain the dependence of δ_p on the host structure reported herein.     

A Novel Type of Water-Soluble Chiral Phosphines Synthesis of Individual RR-and SS-Enantioisomers of Dipotassium 1,3-Di{Phenyl(Carboxylato)Methyl}-5-Phenyl-1,3,5-Diazaphosphorinane

Abstract

The last decade rapid development of catalytic reactions in organic solvent -water bifase systems, especially enantioselective processes, focused the attention of chemists on the synthetic roads to the chiral water-soluble phosphine ligands The reaction of bis(oxymethy1)phenyl-phosphine, paraform and (R)- or (S) α aminoacides open a road to a numerous chiral heterocyclic phosphines and their transition metal complexes with high water solubility.     

Direct Chromatographic Resolution of P-Chiral Organophosphorus Compounds at Analytical and Preparative Levels

Abstract

High-performance liquid chromatography utilizing chiral stationary phases (CSPs) is well established as a very simple and efficient method for obtaining discrete amounts of optically active compounds with high e.e., as well as for determining their enantiomeric composition We wish to demonstrate in the present work that a totally synthetic brush-type π-acidic CSP based on a bis(N,N′-3,5-dinitrobenzoyl) derivative of (R,R)- or (S,S)-trans-1,2-diaminocyclohexane as selector can be used successfully to resolve variety of chiral organophosphorus compounds containing stereogenic centers at phosphorus     

New Efficient Route to the Synthesis of Enantiopure (+) and (−) Bicyclo[2.2.1]heptan‐syn‐2,7‐diol using Lipase‐Catalyzed Transesterifications

Abstract

Starting from racemic 7,7‐dimethoxy‐1,4,5,6‐tetrachlorobicyclo[2.2.1]hept‐5‐en‐2‐endo‐ol (±)‐7, using lipase‐catalyzed transesterification and a series of standard procedures, we prepared the enantiomers (+)‐(2R, 7S) and (?)‐(2S, 7R) bicyclo[2.2.1] heptan‐2,7‐syn‐diol 3 through a new alternative route with excellent yields and enantiomeric excess (up to 99%). These chiral bidentate compounds possess very rigid molecular structures and a favorable stereochemistry for metal coordination, thus becoming promising chiral ligands for asymmetric synthesis.     

Chalcogen Chiral Ylides for the Catalytic Asymmetric Epoxidation of Aldehydes: From Sulfur to Selenium and Tellurium

Abstract

The reaction of novel chiral selenonium and telluronium ylides was investigated with aldehydes and compared to the sulfur analogues. (2R,5R)-2,5-Dimethylselenolane was prepared and reacted as a catalyst for the benzylidenation of aldehydes. Disubstituted epoxides were readily prepared with a (surprising) absence of diastereoselectivity, and with enantiomeric excesses higher than 90%. The reaction of a tellurium analogue, (2S,5S)-2,5-diethyltellurolane, afforded the oxirane in very moderate yield and e.e.'s in the range of 62–82%. Though this was less productive, it is the first report of a chiral telluronium ylide leading to an asymmetric epoxidation of aldehydes.