Thesis (Ph.D.)--University of Wyoming, 2008. / Title from PDF title page (viewed on August 3, 2009). Includes bibliographical references (p. 125-129).

Thesis (Ph. D.)--University of Chicago, Dept. of Chemistry. / Includes bibliographical references. Also available on the Internet.

This thesis presents the development and application of bifunctional iminophosphorane (BIMP) organocatalysts, incorporating a triaryl-substituted iminophosphorane organosuperbase for organocatalytic enantioselective reactions. Chapter 2 describes the design and synthesis of a new class of BIMP catalysts and its application in the first organocatalytic enantioselective sulfa-Michael reaction of alkyl thiols to unactivated β-substituted α,β-unsaturated esters. The conjugate adducts were obtained in up to 94% yield and 94% ee. In addition, the reaction was performed on a 1 gram preparative scale with 1 mol% catalyst. Chapter 3 describes the application of BIMP catalysts in the enantioselective desymmetrisation reaction via an intramolecular Michael addition of a pendant pronucleophile to prochiral cyclohexadienone. The high Brønsted basicity of BIMP catalysts was demonstrated in the Michael addition of high pKa pronucleophiles, such as a-substituted malonamate and amide. Chapter 4 describes the application of BIMP catalysts in the challenging Michael addition of malonates to crotonates, cinnamates and methacrylates. For example, the conjugate adduct of malonate and hexafluoroisopropyl cinnamate was achieved in 91% yield and 63% ee in 48 h.

No description available.

No description available.

A six-step synthesis of salbutamol from methyl salicylate with an overall yield of 17% has been completed, although the yield was not optimised. In the process, Zn(BH4)2 was found to selectively reduce a ketone carbonyl group in the presence of an ester unit. In contrast, borane was found to reduce both the ketone and ester carbonyl groups. Reduction of phenacyl bromide with borane in the presence of chiral catalysts based on (R)-alaninol and (R,S)-ephidrine resulted a measure of enantioselectivity in the product. However, the configuration of the alcohol obtained in the case of (R)-alaninol was contrary to expectations based both on experimental trends observed elsewhere as well as our own theoretical predictions. The asymmetric reduction of methyl 5-bromoacetyl-2-benzyloxybenzoate was accomplished with both borane and Zn(BH4)2 in the presence of a range of chiral catalysts. Optically active products were obtained in all cases, although the optical rotations were significantly smaller in the case of Zn(BH4)2. Unfortunately, we were not successful in determining the enantiomeric excesses of these reactions. The use of a NMR lanthanide shift reagent resulted in a complex spectrum that was impossible to interpret unambiguously. This presumably arises from the presence of several Lewis base sites in the product at which complexation with the shift reagent can take place. It was also not possible to determine the optical rotation of salbutamol itself owing to the relatively small amount of material obtained. A conformational analysis of salbutamol, where NMR data was correlated with molecular modelling results, was successfully carried out and revealed a strong preference for that conformer family characterised by O–C–C–N and Ar–C–C–N torsion angles of ca. 60º and 180º, respectively. Interestingly, these conformers are found to be stabilised by OH…N rather than NH…O hydrogen bonding. This study has also confirmed the effectiveness of the MMFF94 force field for conformational analysis studies in compounds of this kind. Lastly, a relatively simple method for modelling the BH3/oxazaborolidine reduction of ketones at the PM3 semiempirical MO level of approximation was devised. This approach has provided insights into the mechanism of the reaction and has furthermore enabled us to predict the enantioselectivities likely to result from various catalysts and ketones. In comparing our theoretical and experimental findings, an anomalous result was observed in the case of (R)-alaninol; this will have to be investigated further, particularly at the experimental level. However, we believe that our approach provides a sound basis for aiding the design and screening of new, potentially better catalysts.

No description available.

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate: Veronika Skalická Supervisor: Dr. Georgios Paraskevopoulos, Ph.D.; Michael Binnefeld Title of Diploma thesis: Up-scaling and further development of matrix liposomes The thesis evaluates novel matrix liposomes formed by dual asymmetric centrifugation technology. Particles' parameters (size, size distribution and ζ-potential) were analyzed by dynamic light scattering method using ZetaSizer device. Encapsulation efficacy was determined by size exclusion chromatography using carboxyfluorescein as fluorescent encapsulation marker. The overall results support that the most beneficial formulation parameters are 15 min of speed mixing process with ceramic beads of diameter 1,0-1,2 mm. Up-scaling of the procedure didn't drastically affect liposomal parameters up to a lipid batch load of 700 mg. Furthermore, the usage of different types of gelatin or glycerinated gelatin didn't significantly influenced particles' characteristics. It is noteworthy that the matrix composed of 50% glycerinated gel sustained the ability to form liposomes by dispersion of vesicular phospholipid gels in phosphate buffer saline even after 31 days. Other matrices showed a damage of liposomes as confirmed by size and size...

No description available.

A broadly based approach has been undertaken to the development and use of camphor derivatives as chiral auxiliaries in asymmetric synthesis – an approach which has embraced synthetic, mechanistic and computational studies. The unambiguous characterization of mono- and dihydroxy-derivatives, obtained by reduction of chiral camphor ether dimers, has been achieved through detailed one- and two-dimensional NMR spectroscopic analysis. The resulting data has been used to establish both the regio- and stereochemistry of the hydroxyl groups. A camphor-derived cyclic iminolactone has been shown to provide a convenient platform for the synthesis of chiral α-amino acids, stereoselective monoalkylation of the iminolactone affording a range of products in yields of 52 - 65 % with up to 85 % d.e. The attempted development of chiral bifunctional Morita-Baylis-Hillman substrates has revealed an unexpected equilibration between isomeric bornane 2,3-diol monoacrylates via acid-catalysed intramolecular transesterification. A detailed [superscript 1]H NMR-based kinetic study of the rearrangement in various media and at various temperatures has permitted the determination of the kinetic and thermodynamic parameters. A computational study at the DFT level has been used to explore the potential energy surfaces of the acid-catalysed and uncatalysed transesterification of the monoacrylate esters. The theoretical data supports the involvement of cyclic intermediates and has provided a rational basis for predicting the favoured reaction pathways. Novel camphor-derived phenyl sulfonate esters and N-adamantylsulfonamides have been synthesised for use as chiral auxiliaries in the Morita-Baylis-Hillman reaction. Modeling at the Molecular Mechanics level has provided useful insights into possible conformational constraints and an adamantyl sulfonate auxiliary has been successfully used in the stereoselective synthesis of a range of products, generally in excellent yield and with up to 95 % d.e.