No description available.

No description available.

No description available.

No description available.

The use of (S)-methylmandelate as a Chiral Derivatising Agent for chiral acids is described. The diastereoisomers obtained by esterification are studied by (^1)H.N.M.R. Assignment of absolute configuration in these systems is made using models proposed to explain the origin of diastereotopic methylene proton non-equivalence in camphanamides. The development and application of chiral phosphine platinum (O) and palladium (O) ethene complexes as Chiral Derivatising Agents for chiral alkenes and allenes is reported. The (^31)P N.M.R. spectra recorded for the mixtures of diastereo isomers obtained when the ethene ligand is displaced "in situ" by alkene or allene enantiomers are fully described. Efforts to produce a chiral sulphoxide solvating agent for amines, amides and alcohols proved inconclusive. Enantiomerically enriched 2-Naphthyl- and 9-Anthrylmethyl-sulphoxides were synthesised but neither induced non- equivalence in racemic solvates.0-Acetylmandelic acid has been used as a Chiral Solvating Agent for amines and B-aminoalcohols. Diastereomeric salts formed "in situ" are studied by (^1) H N.M.R The accuracy of the integrated enantiomeric composition measurement is ±2% and the sense of chemical shift non-equivalence is consistent with configuration within related series of compounds.

This thesis describes the synthesis, characterization and study of a series of organometallic compounds which all contain the same new ligand, l-phenyl-3-methyl-4,5,6,7-tetrahydroindenyl. The ligand forms a chiral complex once coordinated, and is relatively bulky when compared with ligands such as cyclopentadienyl or 4,5,6,7-tetrahydroindenyl.Chapter one of this thesis introduces cyclopentadienyl ligand chirality, cyclopentadienyl metal complex chirality and sterically demanding cyclopentadienyl systems. The synthesis and chemistry of tetrahydroindenes and some applications of chiral cyclopentadienyl metal complexes and their bulky analogues are also reviewed. Chapter two describes modifications to a literature preparation of the tetrahydroindenone precursor of the new tetrahydroindenyl ligand which lead to higher yields. The synthesis of the ligand itself is described, as well as the synthesis of a benzylidene-substituted hexahydroindene, which demonstrates a limitation in the flexibility of the synthetic route chosen. The synthesis, characterization and various properties of the following iron(II) compounds are discussed in chapter two; bis-l-phenyl-3-methyl- 4,5,6,7-tetrahydroindenyl iron (II), 2.3, l-phenyl-3-methyl-4,5,6,7-tetrahydroindenyl iron(II) dicarbonyl dimer, 2.4, and l-phenyl-3-methyl-4,5,6,7-tetrahydroindaiyl methyl dicarbonyl iron(II), 2.5. For all these iron complexes, the solid state molecular structures and the absolute configuration of the chiral ligand were determined using single crystal X-ray d iffraction. For 23 and 2.4, three isomers are possible, two enantiomers that are collectively termed the rac-isomer and a third isomer, the meso- isomer. Cyclic voltammetric studies on 2.3 indicate that it has a reversible one electron oxidation at 0.187 V (with respect to a non-aqueous Ag/AgCl standard electrode). The difference between this and the reversible one electron oxidation for (η-C(_5)H(_5))(_2)Fe (with respect to the same standard) is -0.314 V, therefore 2.3 is shown to be much more easily oxidized than (η-C(_5)H(_5))(_2)Fe. The solution-state infi-a-red spectrum of 2.4 is explained, with reference to a literature analysis of the unsubstituted analogue [CpFe(CO)(_2)](_2). The steric forces present in the various molecular environments are discussed in connection with the degree of phenyl-ring tilt relative to the cyclopentadienyl mean plane and the deviation of the other cyclopentadimyl substituents away from the metal centre. Subsequent reactions of compounds 2.4 and 2.5 are described. Attempts to make linked analogues of the new ligand are summarized in chapter two. In chapter three, two Zr(rV) compounds are prepared, bis (l-phenyl-3-methyl-4,5,6,7-tetrahydroindenyi) zirconium(fV) dichloride, 3.1, and bis (l-phenyl-3-methyl-4,5,6,7-tetrahydroindenyl) dimethyl zirconium(TV), 3.2. Upon crystallization, rac-3.1 spontaneously resolves into crystals containing only one enantiomer. The similarities and differences in the spectroscopic data for the iron(n) compounds of chapter two and the zirconium(IV) compounds of chapter three are discussed and possible explanations offered . The solid state molecular structures of 3.1 and 3.2 were determined by single crystal X-ray diffraction. Experimental details are given in chapter four, whilst the characterizing data are presented in chapter five. Details of the X-ray structure determinations are given in Appendix A.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes bibliographical references.

The enantiomeric discrimination properties of a number of commercial chiral HPLC stationary phases have been examined using a series of 2-aminotetralin analogues. The mobile phase conditions for each column were varied in order to optimise the separation for the largest number of analytes. Factorial experimental design techniques were used to test the empirically derived mobile phase combinations. A primary limitation of factorial design optimisation strategies, the number of experiments required, was overcome by the development of a simultaneous factorial design method utilising the selectivity of mass spectrometric detection. This enabled the optimisation of the separation of the enantiomers of 12 compounds, using Chiral AGP, to be carried out concurrently. None of the columns tried was able to separate the enantiomers of more than half the analytes. The retention mechanism of the Chiral AGP column was shown to be via cation exchange and non-polar interactions. The ability to form a hydrogen bond between the carbon 8 substitution (acceptor) of the analyte and the stationary phase (donor) was found to be a prerequisite for the separation of enantiomers using Chiral AGP and Chiralcel OD. Neither a rule based nor a mathematical model constructed from calculation derived physicochemical and molecular data were sufficient to describe the enantioselectivity of the Chiral AGP stationary phase. A molecular graphics template model was used to demonstrate the importance of the spatial position of the hydrogen acceptor to the enantioselectivity of the column. Two 2-aminoteralins substituted at the carbon 8 position with a keto-pyrrol function were found to be enantioselectively cleared from in-vitro rat liver preparations dependent upon the substitutions attached to the carbon 2 nitrogen. Differences between these closely related structures were shown to be related to the hydroxylation of the parent molecule, probably, although not exclusively, via the cytochrome P450 isozyme CYP2D6. An in-vivo study using an intravenous dose route showed no sign of enantioselectivity or evidence of the major in-vitro metabolite.

Chiral perturbation theory allows us to probe the low energy properties of hadrons. In this thesis we have looked at the axial coupling constant (see chapter 4) and baryon number violation (see chapter 5).We calculated the axial coupling constant up to O(p^4) using the extended on mass shell renormalisation scheme in chiral perturbation theory. We also included the decuplet as an explicit degree of freedom. To fit the free parameters in our expression we used a combination of lattice and experimental data. We found that the fourth order corrections were quite large, and we struggled to produce an acceptable fit to the data. We also saw that the running of g_{A}^{pn} with M_\pi predicted by lattice QCD and ChPT at O(p^4) do not agree well. This is likely due to a combination of finite size effects impacting the low pion mass lattice data and the chiral perturbative series converging slowly. For our work on baryon number violation we looked at determining the values of two low-energy constants that appear in the baryon violating chiral Lagrangian. To do this, we matched our expression to lattice data. Previous determinations of the parameters had been done without calculating the effect of loops, ours was the first investigation to see what impact the loop diagrams would have. We found that our determinations of the parameters were in agreement with previous results, suggesting the effect of the loops is small. We also performed a chiral extrapolation, and found that our results were in agreement with previous results that did not account for loop corrections. This suggests that the impact of higher-order corrections is not significant for this baryon-number-violating process.

Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Bc. Martin Novák Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: Mgr. et Mgr. Rafael Doležal, Ph.D. Title of diploma thesis: Optimization of chromatographic parameters for chiral separation of biologically active compounds. The diploma thesis was focused on the development of a HPLC-UV method for the determination of K 1277 enantiomers of systematic name N-(2-((6-chloro-1,2,3,4-tetra- hydroacridin-9-yl)amino)hexyl-2-amino-3-(1H-indole-3-yl) propylamide dihydrochloride, which is one of the compounds from the tacrine-tryptophan hybrids group. These tacrine-tryptophan hybrids could be considered as promising candidates of potential drugs against Alzheimer's disease. The thesis brings an explanation of basic characteristic of chiral molecules, principles of chiral separation, pathophysiology, clinical manifestation and treatment of Alzheimer's disease and short characteristic of tacrine-tryptophan hybrids in the theoretical section. The aim of my diploma thesis was to find the optimal chromatographic conditions for separation of K 1277 enantiomers synthesized from tacrine and tryptophan fragments. The experimental part deals with the development of the chiral...