Synthetic studies on prostaglandins: "synthesis of a new thia-PGEI analog"

A PGE1 analog, namely (±)-trans-2-(6'-carbomethoxyhexyl)-3- (E-3"-thia-1 "-octene)-4-hydroxycyclopentanone 71, has been prepared for the first time. Towards the synthesis of this compound, several synthetic approaches aimed at the preparation of the required acetylenic and E-halovinylic sulfides as building blocks were investigated. Among all the methods examined, it appeared evident that the best route to ethynyl n.pentyl sulfide 81 is via a double dehydrohalogenation of the corresponding 1,2-dibromoethyl sulfide with sodium amide in liquid ammonia. In addition, the isomerically pure E-2-iodoethenyl n.pentyl sulfide 85 is conveniently prepared in high yield and stereoselectivity by hydrozirconation-iodination of the terminal ethynyl sulfide 81. The classical hydroalumination and hydroboration reactions for the preparation of vinyl halides from alkynes gave only small yields when applied as methods towards the synthesis of 85 . The building block 2-(6'-carbomethoxyhexyl)-4-hydroxy-2- cyclopentenone (±)-1 carrying the upper side-chain of prostaglandin E 1 was prepared by a step-wise synthesis involving transformations of compounds possessing the required carbocyclic framework (see scheme 27). The synthesis proved to be convenient and gave a good overall yield of (±)-1 which was protected as the TH P-derivative 37 or the siloxy derivative 38. With the required building blocks 81 and 37 in hand, the target 1S-thia-PGE1 analog (±)-71 was prepared via the in situ higher cuprate formation-conjugate addition reaction. This method proved to be convenient and stereospecific. The standard cuprate method, involving an organocuprate reagent generated from an isolated vinyl iodide, did not work well in our case and gave a complicated mixture of products. The target compound will be submitted for assessment of bio log ical activity.

The suppression of the Haller-Bauer scission for synthetic purposes /|nby S. M. Vines. -- 260 St. Catharines, Ont. : [s. n.],

A number of 2-chlorobenzophenones, containing electron releasing groups (e.g. hydroxy, thiomethoxy and methoxy) in the 4' - position, were prepared by the Friess rearrangement, or the Friedel-Crafts reaction. These ketones, when treated with potassamide in liquid ammonia, underwent partial Haller-Bauer scission, unlike 2-chlorobenzophenone which is known to undergo complete scission. Under similar conditions 4-nitrobenzophenone also underwent partial scission, but the main reaction in this case was nucleophilic amination of the nitro containing ring. This amination reaction was shown not to be a useful general reaction for aromatic nitro compounds. 3-Methylxanthone was then prepared by treatment of 2- and 3- chloro-2'-hydroxy-5'-methylbenzophenone with . little, if any, attendant scission. The corresponding 2fluoro- compound also gave the xanthone, but as the 3-fluoro compound did not, it was concluded that the 2-fluoro compound reacted through a nucleophilic substitution mechanism, rather than the benzyne mechanism invoked for the chloro and bromo compounds. 3-Methylthioxanthone was synthesised by treatment of methyl 4-tolyl sulphide and 2-chlorobenzoyl chloride with aluminum chloride in carbon disu1phide, followed.by heating. This compound was also prepared by treatment of 3-chloro-2'thiomethoxy- 5'-methylbenzophenone with potassamide in liquid ammonia.

Transfection of newt blastema mesenchyme using the techniques of lipofection and direct gene transfer

The regenerating amphibian limb provides a useful system for studying genes involved in the establishment of positional information. While a number of candidate genes that may playa role in pattern formation have been identified, their function in vivo is unknown in this system. To better ascertain the role of these genes, it would be useful to be able to alter their normal patterns of expression in vivo and to assess the effects of this misexpression on limb pattern. In order to achieve this, a method of introducing a plasmid containing the eDNA of a gene of interest into a newt blastema (a growth zone of mesenchymal progenitor cells) is needed. Unfortunately, most commonly used transfection techniques cannot be used with newt blastema cells. In this study, I have used the techniques of lipofection and direct gene transfer to introduce plasmid DNA containing reporter genes into the cells of a regenerating newt limb. The technique of lipofection was most effective when the blastema cells were transfected in vitro. The optimal ratio for transfection was shown to be 1:3 DNA:Lipofectin (W/w) , and an increase in the amount of DNA present in the mixture (1:3 ratio maintained) resulted in a corresponding increase in gene expression. The technique of direct gene transfer was used to transfect newt blastema cells with and without prior complex formation with Lipofectin. Injection of plasmid DNA alone provided the most 3 promising results. It was possible to introduce plasmid DNA containing the reporter gene ~-galactosidase and achieve significant gene expression in cells associated with the injection site. In the future, it would be interesting to use this technique to inject plasmid DNA containing a gene which may have a role in pattern formation into specific areas of the newt blastema and to analyze the resulting limb pattern that emerges.

A G. C./M. S. study of the reaction and decomposition products of pentafluorophenyl-grignard and lithium reagents

Decomposition and side reactions of, and the synthetic use of, pentafluorophenylmagnesium bromide and pentafluorophenyllithium have been investigated using G,C9/M.S, techniques• Their reactions with reagents such as CgF^X (X - H, F, CI, Br, 1), C6F4X2 (X - H, CI)f C6F3C13, C6H6. (CgX5)3P (X = H, F), (C6X5)3P=0 (X = H, F), (CgX5)Si (CH3)3 (X = H, F) and (CH0K SiCl , n = 1,2, in ether or ether/n-hexane were studied• In addition to the principal reaction of synthetic use, namely the replacement of a halogen by a pentafluorophenyl group, two types of side reactions were observed* These were (i) intermolecular loss of LiF via a nucleophilic substitution, and (ii) intramolecular loss of LiF, followed by the addition of either inorganic salts such as lithium or magnesium halides, or organometal compounds such as organolithium or organo-Grigaard* G.C«/M.S. techniques were routinely employed to study complicated reaction mixtures. Although mass spectrometry alone has disadvantages for the identification of isomers, deduction of the most probable pathway often helps overcome this problem.

Remembering Lessons Learned: knowledge management techniques for building generational memory

A presentation made at the CAUT Librarians Conference in Ottawa, Ontario in October 2005.

Iridium(I) complexes of phenanthroline-derived benzimidazolylidenes : synthetic, structural and catalytic studies

N-heterocyclic carbenes (NHCs) have undergone rapid development in recent years. Due to their strong a-electron donation and structural variability properties, NHCs are becoming a major class of ligands in organometallic chemistry. Compared with the other two types of NHCs (imidazolylidenes and imidazolinylidenes), benzimidazolylidenes have not been well represented. Limited synthetic approaches may impede the development ofbenzimidazolylidenes. This thesis is focused on the synthesis of phenanthroline-derived benzimidazolylidene ligands and their metal complexes. A series of benzimidazolylidene-iridium complexes were synthesized and characterized spectroscopically and crystallographic ally. All of the new complexes showed varying degrees of catalytic activity and enantioselectivity toward transfer hydrogenation and asymmetric hydrogenation. The best results were achieved in hydrogenation of methyl-2-acetamidoacrylate, which afforded (-)-(R)-methyl-2-acetamidopropanoate in 97% yield and 81 % ee.

Leisure connections : a case study to understand facilitation techniques with survivors of trauma

Leisure-based therapy is a potentially effective approach to supporting survivors of trauma in their healing. The purpose ofthis qualitative case study was to describe the recreation therapist's facilitation techniques of Leisure Connections, a unique leisurebased psycho-educational group for survivors of trauma, and explore how the facilitation was experienced by participants. Qualitative case study design, following the methods of Yin (1994) was used. One two week, three session Leisure Connections group was observed. Six participants completed the Group· Therapy Alliance Scale (pinsof & Catherall, 1986) and reflection cards. In-depth, semi-structured interviews were conducted with the recreation therapist and four participants. Six themes emerged describing group leader interventions, recreation therapist's actions, recreation therapist's preparation and reflections, group members' experience of a therapeutic alliance, group cohesion, and prior influences and assumptions. Therapeutic alliance and group cohesion were influenced by the recreation therapist's group leader interventions (drawing out, processing, protecting) and actions. The context of the group within a therapeutic community milieu was an important influence.

Characterizing Dynamic Optimization Benchmarks for the Comparison of Multi-Modal Tracking Algorithms

Population-based metaheuristics, such as particle swarm optimization (PSO), have been employed to solve many real-world optimization problems. Although it is of- ten sufficient to find a single solution to these problems, there does exist those cases where identifying multiple, diverse solutions can be beneficial or even required. Some of these problems are further complicated by a change in their objective function over time. This type of optimization is referred to as dynamic, multi-modal optimization. Algorithms which exploit multiple optima in a search space are identified as niching algorithms. Although numerous dynamic, niching algorithms have been developed, their performance is often measured solely on their ability to find a single, global optimum. Furthermore, the comparisons often use synthetic benchmarks whose landscape characteristics are generally limited and unknown. This thesis provides a landscape analysis of the dynamic benchmark functions commonly developed for multi-modal optimization. The benchmark analysis results reveal that the mechanisms responsible for dynamism in the current dynamic bench- marks do not significantly affect landscape features, thus suggesting a lack of representation for problems whose landscape features vary over time. This analysis is used in a comparison of current niching algorithms to identify the effects that specific landscape features have on niching performance. Two performance metrics are proposed to measure both the scalability and accuracy of the niching algorithms. The algorithm comparison results demonstrate the algorithms best suited for a variety of dynamic environments. This comparison also examines each of the algorithms in terms of their niching behaviours and analyzing the range and trade-off between scalability and accuracy when tuning the algorithms respective parameters. These results contribute to the understanding of current niching techniques as well as the problem features that ultimately dictate their success.

Strategies and Techniques for Teaching Children with Learning Disabilities: A Case Study of the Spring Reading Program

This case study explored strategies and techniques in order to assist individuals with learning disabilities in their academic achievement. Of particular focus was how a literacy-based program, titled The Spring Reading Program, utilizes effective tactics and approaches that result in academic growth. The Spring Reading Program, offered by the Learning Disabilities Association of Niagara Region (LDANR) and partnered with John McNamara from Brock University, supports children with reading disabilities academically. In addition, the program helps children increase their confidence and motivation towards literacy. I began this study by outlining the importance of reading followed by and exploration of what educators and researchers have demonstrated regarding effective literacy instruction for children with learning disabilities. I studied effective strategies and techniques in the Spring Reading Program by conducting a qualitative case study of the program. This case study subsequently presents in depth, 4 specific strategies: Hands-on activities, motivation, engagement, and one-on-one instruction. Each strategy demonstrates its effectiveness through literature and examples from the Spring Reading Program.

Changements techniques dirigés dans le commerce international: une comparaison d'approches pour les États-Unis.

Rapport de recherche

Techniques alternatives d'estimation et tests en presence d'erreurs de mesure sur les variables explicatives.

Rapport de recherche

New Education Readers : a synthetic and phonic word method

UANL