Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2017. / This thesis is aimed at the investigation of the chiral discrimination process during diastereomeric salt formation, when selected cinchona alkaloids are exposed to racemic mixtures of tartaric acid derivatives. This research is based on the use of (+)‐cinchonine, (‐)‐cinchonidine, (‐)‐quinidine and (+)‐ quinine, which served as chiral bases, in order to resolve racemates of O,O'‐dibenzoyl‐tartaric acid (DBTA) and O,O'‐di‐p‐toluoyl‐tartaric acid (DTTA). Cinchona alkaloids were selected because of their abilities to form salts with the targeted acids. DBTA and DTTA are commonly used resolving agents to separate racemic bases via diastereomeric salt formation, and they are also commercially available and affordable chiral acids. Results were obtained from all combination but only the experiments with cinchonidine were included in this thesis, namely [CIND+][L‐DBTA‐], 2[CIND+][D‐DBTA2‐], [CIND+][LDTTA‐] and 2[CIND+][D‐DTTA2‐]∙2DMSO∙0.7H2O. Experimental analytical techniques, such as thermal analysis, powder X‐ray diffraction, and single crystal X‐ray diffraction were used to analyze the harvested diastereomeric salts. A correlation of molecular parameters derived from the structures and an investigation of the mechanism, which drives the resolution process were discussed. The thesis also summarizes the findings on 8 inclusion compounds of (‒)‐O,O'‐dibenzoyl‐(2R,3R)‐tartaric acid (L‐DBTA) and (‒)‐O,O'‐di‐p‐toluoyl‐(2R,3R)‐tartaric acid (L‐DTTA) or their racemic mixtures, (rac)‐ DBTA and (rac)‐DTTA, with DMSO and water: (rac)‐DBTA∙H2O, (rac)‐DBTA∙DMSO, L‐DBTA∙H2O, LDBTA∙ DMSO, (rac)‐DTTA∙H2O, (rac)‐DTTA∙DMSO, L‐DTTA∙H2O, and L‐DTTA∙DMSO. The discussed inclusion compounds were obtained serendipitously, as a product of the pre‐screening of suitable solvents to dissolve both the acids and the cinchona alkaloids during the discrimination experiments. Only few crystal structures of solvates of these two tartaric acid derivatives are known up to now, and fewer of these structures do exist when both the racemic and the enantiopure acid encapsulates the same solvent. The synthesis and structural analysis of these inclusion compounds contribute to the pool of available crystal structures when comparing chiral vs. achiral crystal forms of the same compounds.

Title from PDF of title page (University of Missouri--Columbia, viewed on March 1, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Michael Harmata. Vita. Includes bibliographical references.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2005. / Includes bibliographical references. Also available in electronic version.

Thesis (M.S.)--University of Texas at El Paso, 2007. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

This thesis is concerned with the use of kinetic resolution strategies for the preparation of enantiomerically pure materials. Chapter 1 introduces kinetic resolution. The limitations of conventional kinetic resolutions are described and the methods used to overcome these limitations are discussed. Chapter 2 presents a double kinetic resolution strategy where the recovered reactant from the first kinetic resolution is used as starting material in a second kinetic resolution. In the second kinetic resolution the major enantiomer present in the starting material is the faster reacting enantiomer. Application of this double kinetic resolution strategy to the Sharpless epoxidation is shown to enable enhanced product enantiomeric excesses to be obtained. Chapter 3 presents an alternative double kinetic resolution strategy where the product from the first kinetic resolution is used as starting material in a second kinetic resolution. In the second kinetic resolution the major enantiomer present in the starting material is the faster reacting enantiomer. Application of this double kinetic resolution strategy using lipase mediated esterification and hydrolysis reactions is shown to enable enhanced product yields to be obtained. Chapter 4 describes the preparation of an enantiomerically pure 2-substituted monoprotected propan-1,3-diol derivative via combination of an asymmetric synthesis and a kinetic resolution. Chapter 5 describes the preparation of the pheromone sulcatol in enantiomerically pure form via combination of an asymmetric synthesis and a kinetic resolution. Chapter 6 presents an investigation into the structure of lithium(α-methylbenzyl)- benzyl amide. Chapter 7 describes an attempted dynamic kinetic resolution of 2-substituted monoprotected propan-1,3-diol derivatives. Chapter 8 describes an attempted preparation of the iron crotonyl complex E-[(η⁵-C₅H₅)Fe(CO)(PPh₃)(COCH=CHCH₃)] in enantiomerically pure form via enzymic kinetic resolution.

This thesis focuses on the asymmetric reduction of N-protected derivatives of (3S)-3-amino-1-chloro-4-phenyl-2-butanone to their corresponding diastereomeric alcohol products, which are key intermediates in the synthesis of HIV protease inhibitors. Although the stereoselective synthesis of the (S,S) alcohol product is easily achieved, preparing the (R,S) diastereomer is much more challenging. I investigated three diastereoselective reduction processes: 1) Meerwein-Ponndorf-Verley (MPV) reduction, 2) asymmetric transfer hydrogenation, and 3) boron reducing agents. The diastereoselectivity of the MPV reduction still favored the (S,S) product; however, I discovered a significant rate enhancement when the standard catalyst (aluminum isopropoxide) was replaced with aluminum tert-butoxide. Many reaction variables were investigated in the asymmetric transfer hydrogenation reaction and the diastereoselectivity was improved to give a ratio of the desired (R,S) diastereomer to the undesired (S,S) alcohol of 9.5:1. Using chiral oxazaborolidine catalysts, an unprecedented (R,S) to (S,S) ratio of 9.5:1 was achieved. Finally, I investigated the effect of the N-protecting group on the stereoselectivity of the reduction. When the original boc-protecting group was replaced with a phthalimide group, the diastereoselectivity of the MPV reduction was reversed to favor the desired (R,S) product.

Ce travail est consacré à la recherche et au développement de nouvelles molécules à viséepharmacologique en série naphtoquinonique en utilisant des réactions par transfert monoélectroniquede type SRN1 et des cyclisations radicalaires oxydatives induites par l'acétate de manganèse(III). Lapremière partie décrit l’étude de la réactivité SRN1 de la 2-(chlorométhyl)-3-méthoxynaphtoquinoneavec divers anions nitronates conduisant à la formation de produits de C-alkylation avec de bonsrendements. Ces derniers ont fait l’objet d’une réaction de réduction-cyclisation permettant la synthèsede nouveaux dérivés benzo[g]indol-5(3H)-ones. Dans la seconde partie, une nouvelle réactiond’oxydation initiée par l’acétate de manganèse(III) a été développée sur la 2-hydroxy-3-méthylnaphtoquinone dans des conditions opératoires douces. En effet, la réactivité originale de la 2-hydroxy-3-méthylnaphtoquinone avec divers alcènes aromatiques en présence de Mn(OAc)3 et dedioxygène, a permis pour la première fois en série naphtoquinonique, l’obtention de nouveaux dérivésoriginaux dihydronaphto[2,3-c][1,2]dioxine-5,10(3H,10aH)-diones sous forme d’un mélange dediastéréoisomères à potentialités antipaludiques. Un mécanisme réactionnel original a été proposé pourla formation de ces produits. / This work is focused on the research and development of new pharmacologicalmolecules in naphthoquinonic series, synthesized by single electron transfer reaction SRN1 ormanganese(III) acetate catalyzed oxidative radical cyclization. The first part describes the SRN1reactivity of 2-(chloromethyl)-3-methoxynaphthoquinone with various nitronate anions leading to theC-alkylation products. The reduction-cyclization reaction of the latter derivatives allowed us to obtainnew benzo[g]indol-5(3H)-one derivatives. In the second part, a new reaction initiated by Mn(OAc)3 on2-hydroxy-3-methylnaphthoquinone was developed under mild conditions. Indeed, the original reaction of2-hydroxy-3-methylnaphthoquinone with various aromatic alkenes in presence of dioxygen led to newdihydronaphtho[2,3-c][1,2]dioxine-5,10(3H,10aH)-dione derivatives as a mixture of diastereoisomerswith antimalarial potential. An original mechanism was proposed in order to explain the formation ofthese products.