Applications of dihydroarenediols to chemoenzymatic synthesis : approaches to total synthesis of morphine alkaloids

The present studies describe, as a primary goal, our recent progess toward the synthesis of morphine alkaloids from aromatic precursors. Model substrates were synthesized which allowed investigation into Diels-Alder, radical cascade, and palladium-catalyzed bond-forming reactions as possible routes to the morphine alkaloid skeleton. As a secondary objective, three separate series of aromatic substrates were subjected to whole-cell oxidation with Escherichia coli JM 109 (pDTG601), a recombinant organism over-expressing the enzyme toluene dioxygenase. Included in this study were bromothioanisoles, dibromobenzenes, and cyclopropylbenzene derivatives. The products of oxidation were characterized by chemical conversion to known intermediates. The synthetic utility of one of these bacterial metabolites, derived from oxidation of o-dibromobenezene, was demonstrated by chemical conversion to (-)conduritol E.

Letters from the Secretary of War to the Committee of Ways and Means, in relation to the number of Militia called into the public service in 1813, to a provision for paying the bounties and premiums to soldiers lately authorized, and to the strength of the army.--

At head of title: [78].

Enantiodivergent chemoenzymatic synthesis of Balanol and approaches to the synthesis of (+)-Codine

The present thesis reviews the development of a formal enantiodivergent synthesis of the (+)- and (-)-isomers of balanol. This approach commences from a cis-dihydrodiol derived from the enzymatic dihydroxylation of bromobenzene. The stereochemistry of the diol is used to direct the synthesis of two different aziridines, each used in the formal synthesis of one enantiomer of balanol. Also described are several enantioselective approaches to (+ )-codeine. Each strategy begins with the enzymatic dihydroxylation of p-bromoethylbenzene and involves a Mitsunobu inversion and intramolecular Heck reaction as key steps.

Development of thermally stable versions of the Burgess Reagent : approaches to the chemoenzymatic total synthesis of morphine

The present studies describe our recent work on expanding the use of the Burgess reagent and its reaction with oxiranes. Several new variants of the Burgess reagent and its chiral auxiliary version were evaluated for their thermal stability by NMR spectroscopy. Three new versions of the reagent were synthesized and their stability was determined. The reactivity of all five Burgess reagents was compared in a dehydration reaction and reactions with epoxides and diols. Progress toward a chemoenzymatic synthesis of morphine is also included in this report. The synthesis began with the whole cell oxidation of bromobenzene by Escherichia coli JMI09(pDTG601). The preparation of several precursors for a key step involving the lohnson-Claisen rearrangement and progress toward the total synthesis are described.

Conceptions of Quality and Approaches to Quality Assurance in Ontario’s Universities

Many international, political, and economic influences led to increased demands for development of new quality assurance systems for universities. Like many policies and processes that aim to assure quality, Ontario’s Quality Assurance Framework (QAF) did not define quality. This study sought to explore conceptions of quality and approaches to quality assurance used within Ontario’s universities. A document analysis of the QAF’s rationale and structure suggested that quality was conceived primarily as fitness for purpose, while suggested indicators represented an exceptional conception of quality. Ontario universities perpetuated such confusion by adopting the framework without customizing it to their institutional conceptions of quality. Drawing upon phenomenographic traditions, a qualitative investigation was conducted to better understand various conceptions of quality held by university administrators and to appreciate ways in which they implemented the QAF. Three main approaches to quality assurance were identified: (a) Defending Quality, characterized by conceptions of quality as exceptional, which focuses on administrative accountability and uses a hands-off strategy to defend traditional notions of quality inputs and resources; (b) Demonstrating Quality, characterized by conceptions of quality as fitness for purpose and value for money, which focuses on accountability to students and uses centralized engaged strategies to demonstrate how programs meet current priorities and intended outcomes; and (c) Enhancing Quality, characterized by conceptions of quality as transformation, which focuses on reflection and learning experience and uses engaged strategies to find new ways of improving learning and teaching. The development of a campus culture that values the institution’s function in student learning and quality teaching would benefit from Enhancing Quality approaches to quality assurance. This would require holistic consideration of the beliefs held by members of the institution, a clear articulation of the institution’s conceptions of quality, and a critical analysis of how these conceptions align with institutional practices and policies.

Letter to S.D. Woodruff in order to give Mr. Woodruff and idea of how fast the interest payments are made to the company

Letter (incomplete) to S.D. Woodruff in order to give Mr. Woodruff an idea of how fast the interest payments are made to the company. The letter is slightly water damaged. The text is affected, but legible. The signature is missing. Feb. 8, 1883.

Synthetic approaches to syn-diol containing biologically active compounds /

The deoxy derivative of pancratistatin 1.10 was prepared in good yield through the use of a [4+2] Diels-Alder cycloaddition and Bischler-Napieralski cyclization approach. The Bischler-Napieralski cyclization was shown to yield two additional side products 2.9, 2.10, however, under slightly modified hydrolysis conditions, the tetracyclic product 2.11 was obtained exclusively in greater than 84% yield. Initial screening of the di-hydroxylatgd derivative, and the other complementary pair analogue 1.10' previously prepared in our laboratories gave interesting results. Both of these compounds were shown to exhibit cytostatic activity; the mono-alcohol was marginally active while the di-hydroxylated analogue proved to be more potent although one to two magnitudes less potent than pancratistatin itself Human tumour cell line assay results indicated that the di-hydroxylated derivative exhibited selective cytotoxic inhibition in the following cell lines: non-small cell lung cancer line NCI-H226 (ED50 - 0.65 ^g/mL), leukemia cell lines CCRF-CEM (ED30 = 0.55 Hg/mL) and HL-60(TB) (ED50 = 0.89^ig/mL). Our results demonstrated that the pharmacophore is not a mono-alcohol, and that the minimum pharmacophore contains the hydroxyl group at the C4 position in addition to either, or both, of the hydroxyl groups present at C2 and C3.' The minimum pharmacophore has been narrowed to only three possibilities which are current synthetic targets in several research groups. The controlled Grignard addition to the tartaric acid derived bis-Weinreb amide 1.25 afforded a direct entry to a host of 1,4-diflferentiated tartaric acid derived intermediates (2.12-2.18). This potentially usefiil methodology was demonstrated through the efficient synthesis of the naturally occurring lactone 2.23, which bears the inherent syn-dio\ subunit. Based on this result, a similar approach to the synthesis of syn-dio\ bearing natural products looks very promising? A direct 2,3-diol desymmetrization method using TIPS-triflate was shown to be effective on the selective differentiation of Z,-methyl tartrate (and diisopropyl tartrate). The mono-silyl-protected intermediates 2.31 also proved to be useful when they were selectively differentiated at the 1,4-carboxyl position (2.35, 2.36) through the use of a borohydride reducing agent. Furthermore, the mono-silyl-protected derivative underwent periodate cleavage affording two synthetically useful a,P-unsaturated esters 2.43, 2.44, with one of esters being obtained via a silyl-migration method.''

An in-depth analysis of real and perceived barriers to speech and language program participation for children with speech and language delays : a question of barriers to service?

The current study investigated the effects that barriers (both real and perceived) had on participation and completion of speech and language programs for preschool children with communication delays. I compared 36 families of preschool children with an identified communication delay that have completed services (completers) to 13 families that have not completed services (non-completers) prescribed by Speech and Language professionals. Data findings reported were drawn from an interview with the mother, a speech and language assessment of the child, and an extensive package of measures completed by the mother. Children ranged in age from 32 to 71 mos. These data were collected as part of a project funded by the Canadian Language and Literacy Research Networks of Centres of Excellence. Findings suggest that completers and non-completers shared commonalities in a number of parenting characteristics but differed significantly in two areas. Mothers in the noncompleting group were more permissive and had lower maternal education than mothers in the completing families. From a systemic standpoint, families also differed in the number of perceived barriers to treatment experienced during their time with Speech Services Niagara. Mothers in the non-completing group experienced more perceived barriers to treatment than completing mothers. Specifically, these mothers perceived more stressors and obstacles that competed with treatment, perceived more treatment demands and they perceived the relevance of treatment as less important than the completing group. Despite this, the findings suggest that non-completing families were 100% satisfied with services. Contrary to predictions, there were no significant differences in child characterisfics and economic characteristics between completers and non-completers. The findings in this study are considered exploratory and tentative due to the small sample size.

Application of [Lambda] to the fourth perturbation theory in calculating the equation of state of rare gas solids and fcc metals

We have calculated the thermodynamic properties of monatomic fcc crystals from the high temperature limit of the Helmholtz free energy. This equation of state included the static and vibrational energy components. The latter contribution was calculated to order A4 of perturbation theory, for a range of crystal volumes, in which a nearest neighbour central force model was used. We have calculated the lattice constant, the coefficient of volume expansion, the specific heat at constant volume and at constant pressure, the adiabatic and the isothermal bulk modulus, and the Gruneisen parameter, for two of the rare gas solids, Xe and Kr, and for the fcc metals Cu, Ag, Au, Al, and Pb. The LennardJones and the Morse potential were each used to represent the atomic interactions for the rare gas solids, and only the Morse potential was used for the fcc metals. The thermodynamic properties obtained from the A4 equation of state with the Lennard-Jones potential, seem to be in reasonable agreement with experiment for temperatures up to about threequarters of the melting temperature. However, for the higher temperatures, the results are less than satisfactory. For Xe and Kr, the thermodynamic properties calculated from the A2 equation of state with the Morse potential, are qualitatively similar to the A 2 results obtained with the Lennard-Jones potential, however, the properties obtained from the A4 equation of state are in good agreement with experiment, since the contribution from the A4 terms seem to be small. The lattice contribution to the thermal properties of the fcc metals was calculated from the A4 equation of state, and these results produced a slight improvement over the properties calculated from the A2 equation of state. In order to compare the calculated specific heats and bulk moduli results with experiment~ the electronic contribution to thermal properties was taken into account~ by using the free electron model. We found that the results varied significantly with the value chosen for the number of free electrons per atom.

Aboriginal women in education : Honouring our experiences a vision of access to and success within the university

This thesis explores Aboriginal women's access to and success within universities through an examination of Aboriginal women's educational narratives, along with input from key service providers from both the Aboriginal and non-Aboriginal community. Implemented through the Wildfire Research Method, participants engaged in a consensusbased vision of accessible education that honours the spiritual, emotional, intellectual, and physical elements necessary for the success of Aboriginal women in university. This study positions Aboriginal women as agents of social change by allowing them to define their own needs and offer viable solutions to those needs. Further, it connects service providers from the many disconnected sectors that implicate Aboriginal women's education access. The realities of Aboriginal women are contextualized through historical, sociocultural, and political analyses, revealing the need for a decolonizing educational approach. This fosters a shift away from a deficit model toward a cultural and linguistic assets based approach that emphasizes the need for strong cultural identity formation. Participants revealed academic, cultural, and linguistic barriers and offered clear educational specifications for responsive and culturally relevant programming that will assist Aboriginal women in developing and maintaining strong cultural identities. Findings reveal the need for curriculum that focuses on decolonizing and reclaiming Aboriginal women's identities, and program outcomes that encourage balance between two worldviews-traditional and academic-through the application of cultural traditions to modern contexts, along with programming that responds to the immediate needs of Aboriginal women such as childcare, housing, and funding, and provide an opportunity for universities and educators to engage in responsive and culturally grounded educational approaches.