摘要:

AbstractA comparison of α‐, β and γ‐cyclodextrins in the solid state is made. Monomeric features analyzed include orientations of primary hydroxyl groups and pyran ring pucker. Macromolecular features examined include planarity of the oligomer, tilting of pyran rings, and, deviation from Cnsymmetry wheren= number of monomers. The mean values and standard deviations of these shape descriptors are given for cyclodextrins with and without guests embedded in their interiors. Molecular mechanics calculations using the MM2, AMBER, and CHARMM force fields show that most solid state cyclodextrins are trapped in high‐energy conformations relative to the most stable forms found in this study. © 1992 Wiley

ISSN:0899-0042    

DOI:10.1002/chir.530040402

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe optical stability of gossypol [1,1',6,6',7,7'‐hexahydroxy‐3,3'‐dimetyl‐5,5'‐bis(1‐methylethyl)‐2,2'‐binaphthalene‐8,8'‐dicarboxaldehyde], a natural product exhibiting profoundly enantiospecific antitumor and male antifertility action, was investigated by means of computational methods and thermal racemization experiments. The calculations on gossypol and several derivatives and model compounds were carried out using the MM2 force field; energies and geometries of minimum energy conformations, as well as structures along various inversion pathways, were calculated. According to the calculations, gossypol (the dialdehyde form) and its simple analogues are not thermally racemizable (energy barriers for rotational inversion above 50 kcal/mol). By contrast, the calculations suggest that the acetal tautomer of gossypol and its dehydration product (anhydrogossypol) are thermally racemizable, although the energy barriers are still relatively high (35–40 kcal/mol). Optically pure (+)‐anhydrogossypol was prepared and characterized; its racemization became rapid only at high temperatures (180–200°C). When dehydration of gossypol was hindered (in aqueous solution), no racemization of gossypol was observed after prolonged heating at 90

ISSN:0899-0042    

DOI:10.1002/chir.530040403

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe enantiomers of chlorthalidone (CTD) and a minor, achiral dehydration product, δ2‐CTD, are shown to exist in dynamic equilibrium in aqueous media through a carbonium ion intermediate. The barrier to inversion at carbon is low for an uncatalyzed system: ΔG‡= 21.6 kcal/mol. This behavior extends to other 3‐hydroxy‐3‐phenylphthalimidines (HPPs), with formation of the analogous Δ2‐HPP blocked by alkyl substitution at the 2‐nitrogen. © 199

ISSN:0899-0042    

DOI:10.1002/chir.530040404

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractLong standing errors in major pharmacopoeiae (BP,USP, and Eu.Ph.) concerning the absolute stereochemistry of the widely used antituberculosis drug (+)‐ethambutol have been clarified by unambiguous synthesis and chiral HPLC. on a Pirkle, covalentD‐phenylglycine column of perbenzoyl derivatives of each stereomer; the enantiomeric (−)‐(R,R) and (+)‐(S,S)‐ethambutols together with the optically inactive (meso)‐(R,S)‐ethambutol. This paper describes how circular dichroism (CD) alone and combined with HPLC is used to demonstrate this chiral separation and also to confirm the absolute stereochemistry of each stereomer of ethambutol and its synthetic precursor 2‐aminobutan‐1‐ol from studies of „exciton coupling.”︁ The strengths and weaknesses of these chir

ISSN:0899-0042    

DOI:10.1002/chir.530040405

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe synthesis of the eight stereoisomers of muscarine has been efficiently accomplished by utilizing the two enantiomers of lactic esters as starting material. The synthetic strategy is based on a SnCl4‐catalyzed addition of allyltrimethylsilane to O‐protected lactic aldehydes followed by an iodocyclization process. All the final derivatives possess an enantiomeric excess higher than 98%. The four pairs of enantiomers bound to M1, M2, and M3muscarinic receptor subtypes in membranes from cerebral cortex, heart, and salivary glands, respectively, and recognized heterogeneous states of the receptors. Of the eight isomers, only natural muscarine (+)‐1recognized three affinity states of the M2receptor. The compound was also the only one to show selectivity in the binding study, demonstrating 37‐ to 44‐fold higher affinity for the M2than for the M1or M3receptors. In addition, the compounds were tested in functional assays on isolated guinea pig atria (M2receptors) and ileum (mixed population of M2and M3receptors) and their muscarinic potencies were determined. Among the eight isomers, again only (+)‐1enantiomer was found to be very active on both tissues. Its potency was more than two orders of magnitude higher than that of its enantiomer (−)‐1as well as the other six isomers. The eudismic ratios (E.R.) deduced from the two functional tests were 324 and 331. © 1992

ISSN:0899-0042    

DOI:10.1002/chir.530040406

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe protein binding of etodolac enantiomers was studied in vitro by equilibrium dialysis in human serum albumin (HSA) of various concentrations varying from 1 to 40 g/liter, by addition of each enantiomer at increasing concentrations. In the 1 g/liter solution, at the lowest drug levels, the (R)‐form is more bound than its antipode, the contrary being observed at the highest drug levels. For higher albumin concentrations, S was bound in a larger extent than R. Using the displacement of specific markers of HSA sites I and II, studied by spectrofluorimetry, it was suggested that R and S are both bound to site I, while only S is strongly bound to site II. © 1992 Wiley‐Liss,

ISSN:0899-0042    

DOI:10.1002/chir.530040407

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe use of enzymes to assay individual components of the L‐carnitine family in pharmaceuticals, foodstuffs, and biological fluids with various forms of detection is reviewed. The most useful enzyme in the assay of compounds of the L‐carnitine family is carnitine acetyl transferase (CAT), which catalyses the reversible interconversion of L‐carnitine and its short‐chain acyl esters. CAT can be used in one or more coupled reactions combined with U.V., or radiolabelled detection, or combined with HPLC, allowing, enantioselective, structurally specific, and, in the case of radiolabelled tracing, highly sensitive assays to be carried out. When compared with chromatographic separation of enantiomers or diastereoisomers, enantioselective enzyme mediated assays may be cheaper, more sensitive, and simpler, but they do not allow the nonpreferred isomer to be assayed. Consequently, they are appropriate for the specific assay of endogenous enantiomeric substrates of the enzyme concerned, in biological samples. The analysis of the other enantiomer in raw materials or in pharmaceuticals must be more properly approached by enantioselective chromatographic

ISSN:0899-0042    

DOI:10.1002/chir.530040408

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe direct enantiomeric separation of a series of β‐blockers has been carried out on two chiral stationary phases (CSPs) derived from 3,5‐dinitrobenzoyl tyrosine: the commercially available ChyRoSine‐A and a recent improved version of this CSP.Using supercritical fluid chromatography (SFC), facile separations are achieved (1.1

ISSN:0899-0042    

DOI:10.1002/chir.530040409

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

Abstractrac‐Methadone is used clinically for the chronic maintenance treatment of heroin addiction and for the relief of pain. As the pharmacological activity of methadone is due primarily to the (−)‐(R)‐enantiomer, stereospecific measurements of methadone serum concentrations in methadone‐treated patients are expected to be more relevant for clinical studies than earlier described total drug measurements. This study describes a stereospecific gas chromatographic (GC) method for the determination of methadone in serum. The extracted methadone was derivatizised with (−)‐menthyl chloroformate. The diastereometric derivatives were analysed by GC on a capillary column and detected with a nitrogen‐phosphorus detector. The resolution factor obtained for the methadone enantiomers was 1.1 with a relatively short time of analysis (30 min). By analysing the pure (−)‐(R)‐enantiomer, no racemization was seen during the analysis. The lower limit of quantitation was 75 nmol/1 for each enantiomer. Measurements of the ratio between (−)‐(R)‐ and (+)‐(S)‐methadone concentrations in serum from five methadone‐treated patients showed interindividual differences (range 0.5–1.1). The patient results correlated well with those from another

ISSN:0899-0042    

DOI:10.1002/chir.530040410

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractEnantiomers of terfenadine were resolved by high‐performance liquid chromatography (HPLC) using a chiral stationary phase (CSP) column packed with β‐cyclodextrin (β‐CD) covalently bound to silica. Separation was achieved in both the reverse phase and normal phase modes. Resolution of enantiomers was confirmed by ultraviolet‐visible absorption, circular dichroism, and mass spectral

ISSN:0899-0042    

DOI:10.1002/chir.530040411

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY