Two Novel Homochiral Enantiomorphic 3D Metal-organic Frameworks:Synthesis,Crystal Structure,Luminescent and SHG Properties

Two homochiral enantiomorphic 3D coordination polymers： （D-HAPA）2[Cd2Cs（D- HAPA）（m-BDC）4]＇（EtOH） （1D） and （L-HAPA）2[Cd2Cs（L-HAPA）（m-BDC）a]＇（EtOH） （1L） （APA = 2-amino-l-propanol, m-H2BDC = 1,3-benzenedicarboxylate）, have been assembled solvothermally respectively with the induction of enantiomorphic organic small molecules （D,L-APA）. 1L and 1I） crystallize in chiral space group P21 with Flack parameters of-0.012（13） and -0.07（3）, respectively, and have been characterized by satisfactory elemental analysis, FT-IR spectra, CD-spectra and single-crystal X-ray diffraction. They both exhibit sqp topological net, purple fluorescence and SHG activity.

Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen,ketoprofen and etodolac binding with HSA

The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin （HSA） was investigated using indirect chiral high performance liquid chromatography （HPLC） and ultrafiltration techniques. S-（-）-1-（1-naphthyl）- ethylamine （S-NEA） was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for the separation and assay of the three pairs of enantiomer. The method had good linear relationship over the investigated concentration range without interference. The average extraction efficiency was higher than 85% in different systems, and the intra-day and inter-day precisions were less than 15%. In serum albumin, the protein binding of etodolac enantiomers showed significant stereoselectivity that the affinity of S-enantiomer was stronger than R-enantiomer, and the stereoselectivity ratio reached 6.06; Flurbiprofen had only weak stereoselectivity in HSA, and ketoprofen had no stereoselectivity at all. Scatchard curves showed that all the three chiral drugs had two types of binding sites in HSA.

Significance and challenges of stereoselectivity assessing methods in drug metabolism

Stereoselectivity in drug metabolism can not only influence the pharmacological activities, tolerability, safety, and bioavailability of drugs directly, but also cause different kinds of drug-drug interactions. Thus, assessing stereoselectivity in drug metabolism is of great significance for pharmaceutical research and development （R＆D） and rational use in clinic. Although there are various methods available for assessing stereoselectivity in drug metabolism, many of them have shortcomings. The indirect method of chro- matographic methods can only be applicable to specific samples with functional groups to be derivatized or form complex with a chiral selector, while the direct method achieved by chiral stationary phases （CSPs） is expensive. As a detector of chromatographic methods, mass spectrometry （MS） is highly sen- sitive and specific, whereas the matrix interference is still a challenge to overcome. In addition, the use of nuclear magnetic resonance （NMR） and immunoassay in chiral analysis are worth noting. This review presents several typical examples of drug stereoselective metabolism and provides a literature-based evaluation on current chiral analytical techniques to show the significance and challenges of stereo- selectivity assessing methods in drug metabolism.

Asymmetric Photocatalyzed Addition of Cyclic Ammes to the Chiral 5-(l)-Menthyloxy-2(5H)-furanone

The benzophenone-initiated photoaddition of N-methyl ammes 2 to the chiral synthon1 proceeds in a regiospecitlc and highlyr stereocontrolled thshion to give the C-C photoadductscontaining a ne\viy stereogenic center 3a-3c. The enantiomerically pure N-C photoadducts, aminobutenolides 5a-5c have been obtained from the enantioselective photoaddition of secondary cyclicammes 4 with the chiral synthon 1 under the same conditions.

Separation of Enantiomers of Clopidogrel on Chiral Stationary Phases by Packed Column Supercritical Fluid Chromatography

A packed column supercritical fluid chromatography (SFC) method for the separation of clopidogrel enantiomers on a chiral stationary phase and CO2 with modifier as mobile phase has been developed at an analytical scale. Among 11 different 2 stationary phases the Chiral cel OD-H column showed by far the best separation properties. The influence of different modifiers, injection solvents, temperature, and pressure, and density of the fluid, respectively, on the separation behaviour has been studied. It was found that the separation behaviour strongly depends on the type of modifier and the modifier content. Temperature and pressure are of less influence.

Chiral Separation of Erythromycin as a New Chiral Selector on CE

Erythromycin as a new chiral selector was first used for chrial separation of four derivatives of biphenyldimethylester enantiomers on CE. The influence of pH, the chiral selector concentration and organic modifiers were preliminarily studied. Experiments show that the erythromycin as chiral selector is useful to CE.

Direct Enantiomer Separation of 2-PhenylcyclopropanecarboxylateEsters on Cyclodextrin Derivatives Stationary Phases in GC

Direct enantiomeric separation of all four optical isomers of 2-phenylcyclopropane carboxylate ester was first achieved on each of the three different beta-cyciodextrin chiral stationary phases (CSPs) in GC. Using these CSPs, enantiomeric excess of the products of enantioselective cyclopropanation can be determined directly, conveniently and fast.

Silylated and acetylated β-cyclodextrins for gas chromatographic stationary phases

Two new chiral stationary phases, 2,3 di O acetyl 6 O trimethylsilyl β cyclodextrin (DATBCD) and 2,6 di O trimethylsilyl 3 O acetyl β cyclodextrin(DTABCD), were synthesized, their structures were identified by means of infrared and NMR spectra. Capillary columns were coated with the two stationary phases by dynamic method. The chromatographic properties, and enantiomers separation, such as ketone, esters, alcohols and olefines, were investigated on the silylated and acetylated β cyclodextrin stationary phases. The experimental results show that the silylated and acetylated β cyclodextrins are suitable to be used as capillary gas chromatographic stationary phases, the relative polarity of DATBCD and DTABCD stationary phases is respectively 4143 and 3928, the column efficiencies are respectively 3084 and 4198, and DATBCD is of stronger enantioselectivity than DTABCD, capacity factor of the first eluted enantiomer ( k 1) and separation factor(α)of α phenylethanol on DATBCD stationary phase are respectively 8.23 and 1.019.

Preparation of insoluble β-CD polymer and its application to enantiomers and isomers separation

An insoluble β cyclodextrin polymer cross linked with epichlorohydrin was prepared, and its structure was identified with infrared spectrum. Colloid stationary phase was prepared by dissolving the polymer in the mixed solvent of diisopropyl ether, methylene dichloride and benzene and treated for 0.5 h by ultrasonication, and then was coated on a fused silica capillary column. The optimun reaction conditions are as follows: the mole ratio of epichlohydrin to β cyclodextrin is 12.1∶1, reacting at 65 ℃ for 24 h. The Chromatographic performance such as column efficiency, thermal stabilities and polarity were studied, two kinds of disubstituted benzene isomers and eight pairs of enantiomers were separated on the capillary column. The results show that the β cyclodextrin polymer is suitable for use as a capillary gas chromatographic stationary phase, and possess excellent chromatographic properties in separating enantiomers and position isomers.

Proposed Extension to the Natta Projection Notation System for Enabling an Indication of Relative Stereochemistry and the Stereochemical State

A system of structure depiction, as an extension of the wedge and hashed wedge bonds (Natta projection), and text notation is herein suggested that embodies more explicit information—or reduced over-statement as circumstances warrant—on the stereochemical nature of the system at hand, in particular, for those cases where only the relative stereochemistry of a compound is known.

Syntheses, Crystal Structures, and Biological Activities of Two Enantiomeric 2-Trifluoromethylthieno[2,3-d]pyrimidin-4-amine Derivatives

Two enantiomeric 2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d] pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two chiral amines with 4-chloro-2-trifiuoromethyl-6,7-dihydro-5H-cyclopenta[4~5]thieno[2-3-d]pyrimidine, which started from 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, trifluoroacetic acid （TFA） and phosphoryl trichloride via one-pot procedure. Their structures were determined by single-crystal X-ray diffraction. Enantiomer （R）-3,（R）-N-（1-phenylethyl）-2-trifluoromethyl-6,7- dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P43 with a = 8.6847（6）, b = 8.6847（6）, c = 22.419（2） A, V= 1690.9（3） A3, Z = 4, Dc = 1.428 g/cm^3, p = 0.228 mm-1, F（000） = 752, the final R = 0.0463 and wR = 0.1257 for 3442 observed reflections with 1〉 20（/）. Enantiomer （S）-3,（S）-N-（1-phenylethyl）-2-trifluoromethyl-6,7-dihydro- 5H-cycloperita[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P41 with a = 8.688, b = 8.688, c = 22.421 A, V = 1692.4 A3, Z = 4, Dc = 1.426 g/cm^3, μ= 0.227 mm^-1, F（000） = 752, the final R = 0.0682 and wR = 0.1806 for 3182 observed reflections with ≥20（I）. The preliminary bioassay indicated that the R-enantiomer exhibits higher antitumor activity against MCF-7 than gefitinib.

Screening primary racemic amines for enantioseparation by derivatized polysaccharide and cyclofructan columns

It is a challenge to separate the enantiomers of native chiral amines prone to deleterious silanol interactions. Aset of 39 underivatized chiral primary amines was screened for enantiomeric separation. Seven recentlyintroduced commercial chiral columns were tested. They included six polysaccharide based chiral stationaryphases (CSP) with bonded derivatives, ChiralPak? IA, IB, IC, ID, IE and IF columns and a cyclofructanderivatized CSP, Larihc? CF6-P column. Both the normal phase (NP) mode with heptane/alcohol mobile phasesand the polar organic (PO) mode with acetonitrile/alcohol were evaluated. It was found that the cyclofructanbased CSP demonstrated the highest success rate in separating primary amines in the PO mode with only onechiral amine not resolved. It is shown that, when screening the columns, there is no standard optimal condition;an excellent mobile phase composition for one column may be poorly suited to another one. Althoughbutylamine was a good mobile phase additive for the polysaccharide columns in both PO and NP modes, it wasdetrimental to the enantio-recognition capability of the cyclofructan column. Triethylamine was the appropriatesilanol screening agent for this latter column.

Development of a UHPLC-MS/MS method for the quantification of ilaprazole enantiomers in rat plasma and its pharmacokinetic application

In Korea and China,ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers.In this study,a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma,using R-lansoprazole as the internal standard.The enantioseparation was achieved on a CHIRALPAK AS-RH column(4.6 mm×150 mm,i.d.5 mm),with a mobile phase composed of 10 m M ammonium acetate aqueous solution and acetonitrile(60:40,V/V),at a flow-rate of 0.5 m L/min.The method was validated over the concentration range of 0.5 e300 ng/m L for both,R-and S-ilaprazole.The lower limit of quantification was 0.5 ng/m L for both enantiomers.The relative standard deviation(RSD)of intra-and inter-day precision of R-ilaprazole and S-ilaprazole was less than 10.9%,and the relative error accuracy(RE)ranged fromà0.5%e2.0%.Finally,the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate.

Preparation of Enantiomerically Pure 1,1'-Bi-2-naphthols from 85% Cinchonine and 1,1'-Bi-2-naphtholboric Anhydride

A possibility of preparation of enantiomerically pure 1,1' bi 2 naphthols using an impure cinchonine has been examined. The solid and the mother liquor formed from the reaction of 1,1' bi 2 naphtholboric anhydride and 85 % cinchonine in toluene could give optically pure (S) ( ) and (R) (+) 1,1' bi 2 naphthol after acidification and kinetic crystallization, the overall yields were 40 % and 28 %, respectively.

Enantioselective Total Synthesis of the (+) Antipode of Zeylenone

Starting from shikimic acid, the total synthesis of zeylenone was studied. The productwas proved to be the (+)antipode of zeylenone through analysis and comparison of their respectivespectra (including NMR, MS, IR and CD) and optical data. The absolute configuration of thenatural product was thus determined to be (1S,2S,3R).

A Chiral Phosphorous Derivatizing Agent for the Determination of the Enantiomeric Excess of Chiral Alcohols, Amines by ^(31)P NMR

A chiral phosphorous derivatizing agent prepared from PCl3 and (S)-BINOL was described. It is used to determine the enantiomeric excess of chiral alcohols and amines by 31P NMR.

Synthesis of Novel Chiral Diol Ligands for the Enantioselective Reactions

A series of novel enantiomerically pure diols were synthesized from D-erythorbic acid in three steps, and the absolute configuration of one of them 4a has been confirmed by X-ray analysis.

Using the Chiral Organophosphorus Derivatizing Agents for Determination of the Enantiomeric Composition of Chiral Carboxylic Acids by ^(31)PNMR Spectroscopy

The use of chiral organophosphoras derivatizing agents prepared in situ from chiral tartrate or chiral diamine for the 31PNMR determination of the enantiomeric composition of chiral carboxylic acids is described. The method is accurate, reliable and convenient.