Diastereoselective Lithiation-Substitution of N-Silyl-Protected-(S)-Tetrahydro-1H-pyrrolo[1,2-c]imidazole-3(2H)-ones and Applications of Their Derivatives

This thesis describes a method involving the preparation of an L-proline-derived imidazolone protected with an N-triethylsilyl group that undergoes diastereoselective lithiation followed by electrophile quench to give C5-substituted products with syn stereochemistry. The N-silylated derivatives may be more easily N-deprotected as compared to previous N-t-Bu analogues to give secondary ureas. These may serve as precursors to N-phenyl chiral bicyclic guanidines or as NHC precursors for synthesis of corresponding complexes.

Organizational commitment and perceived relatedness as correlates of the intention to continue officiating in track and field

The objectives of the present study were to explore three components of organizational commitment (affective [AC], normative [NC] and continuance [CC] commitment; Allen & Meyer, 1991), perceived relatedness (Oeci & Ryan, 1985; 2002), and behavioural intention (Ajzen, 2002) within the context of volunteer track and field officiating. The objectives were examined in a 2-phase study. Ouring phase 1, experts (N = 10) with domain familiarity assessed the item content relevance and representation of modified organizational commitment (OC; Meyer, Allen & Smith, 1993) and perceived relatedness (La Guardia, Oeci, Ryan & Couchman, 2000) items. Fourteen of 26 (p < .05) items were relevant (Aiken's coefficient V) and NC (M = 3.88, SO = .64), CC (M = 3.63, SD = .52), and relatedness (M = 4.00, SD = .93) items had mean item content-representation ratings of either "good" or "very good" while AC (M = 2.50, SD = 0.58) was rated "fair". Participants in phase 2 (N = 80) responded to items measuring demographic variables, perceptions of OC to Athletics Canada, perceived relatedness to other track and field officials, and a measure of intention (yiu, Au & Tang, 2001) to continue officiating. Internal consistency reliability estimates (Cronbach's (1951) coefficient alpha) were as follows: (a) AC = .78, (b) CC = .85, (c) NC = .80 (d) perceived relatedness = .70 and, (e) intention = .92 in the present sample. Results suggest that the track and field officials felt only minimally committed to Athletics Canada (AC M = 3.90, SD = 1.23; NC M = 2.47, SD = 1.25; CC M = 3.32; SD = 1.34) and that their relationships with other track and field officials were strongly endorsed (M = 5.86, SD = 0.74). Bivariate correlations (Pearson r) indicated that perceived relatedness to other track and field officials demonstrated the strongest relationship with intention to continue officiating (r = .346, p < .05), while dimensions of OC were not significantly related to intention (all p's > .05). Together perceived relatedness (j3 = .339, p = .004), affective commitment (j3 = -.1 53, p = .308), normative commitment (j3 = -.024, p = .864) and continuance commitment (j3 = .186, P = .287) contribute to the prediction of intention to continued officiating (K = .139). These relationships remained unaffected by the inclusion of demographic (j3age = -.02; P years with Athletics Canada = -.13; bothp's > .05) or alternative commitment (j3sport = -.19; P role = .15; Pathletes = .20; all p' s > .05) considerations. Three open-ended questions elicited qualitative responses regarding participants' reasons for officiating. Responses reflecting initial reasons for officiating formed these higher order themes: convenience, helping reasons, extension of role, and intrinsic reasons. Responses reflecting reasons for continuing to officiate formed these higher order themes: track and field, to help, and personal benefits. Responses reflecting changes that would influence continued involvement were: political, organizational/structural, and personal. These results corroborate the findings of previous investigations which state that the reasons underpinning volunteer motivations change over time (Cuskelly et al., 2002). Overall, the results of this study suggest that track and field officials feel minimal commitment to the organization of Athletics Canada but a stronger bond with their fellow officials. Moreover, the degree to which track and field officials feel meaningfully connected to one another appears to exert a positive influence on their intentions to continue officiating. As such, it is suggested that in order to promote continued involvement, Athletics Canada increases its focus on fostering environments promoting positive interactions among officials.

Vitamin D status and latent tuberculosis infection : a preliminary study in a group of healthy Mexican agricultural workers

Vitamin D metabolites are important in the regulation of bone and calcium homeostasis, but also have a more ubiquitous role in the regulation of cell differentiation and immune function. Severely low circulating 25-dihydroxyvitamin D [25(OH)D] concentrations have been associated with the onset of active tuberculosis (TB) in immigrant populations, although the association with latent TB infection (LTBI) has not received much attention. A previous study identified the prevalence of LTBI among a sample of Mexican migrant workers enrolled in Canada's Seasonal Agricultural Workers Program (SA WP) in the Niagara Region of Ontario. The aim of the present study was to determine the vitamin D status of the same sample, and identify if a relationship existed with LTBI. Studies of vitamin D deficiency and active TB are most commonly carried out among immigrant populations to non-endemic regions, in which reactivation of LTBI has occurred. Currently, there is limited knowledge of the association between vitamin D deficiency and LTBI. Entry into Canada ensured that these individuals did not have active TB, and L TBI status was established previously by an interferon-gamma release assay (IGRA) (QuantiFERON-TB Gold In-Tube®, Cellestis Ltd., Australia). Awareness of vitamin D status may enable individuals at risk of deficiency to improve their nutritional health, and those with LTBI to be aware of this risk factor for disease. Prevalence of vitamin D insufficiency among the Mexican migrant workers was determined from serum samples collected in the summer of 2007 as part of the cross sectional LTBI study. Samples were measured for concentrations of the main circulating vitamin D metabolite, 25(OH)D, with a widely used 1251 250HD RIA (DiaSorin Inc.®, Stillwater, MN), and were categorized as deficient «37.5 nmoI/L), insufficient (>37.5 nmollL, < 80 nmol/L) or sufficient (2::80 nmoI/L). Fisher's exact tests and t tests were used to determine if vitamin D status (sufficiency or insufficiency) or 25(OH)D concentrations significantly differed by sex or age categories. Predictors of vitamin D insufficiency and 25(OH)D concentrations were taken from questionnaires carried out during the previous study, and analyzed in the present study using multiple regression prediction models. Fisher's exact test and t test was used to determine if vitamin D status or 25(OH)D concentration differed by LTBI status. Strength of the relationship between interferongamma (IFN-y) concentration (released by peripheral T cells in response to TB antigens) and 25(OH)D concentration was analyzed using a Spearman correlation. Out of 87 participants included in the study (78% male; mean age 38 years), 14 were identified as LTBI positive but none had any signs or symptoms of TB reactivation. Only 30% of the participants were vitamin D sufficient, whereas 68% were insufficient and 2% were deficient. Significant independent predictors of lower 25(OH)D concentrations were sex, number of years enrolled in the SA WP and length of stay in Canada. No significant differences were found between 25(OH)D concentrations and LTBI status. There was a significant moderate correlation between IFN-y and 25(OH)D concentrations ofLTBI-positive individuals. The majority of participants presented with Vitamin D insufficiency but none were severely deficient, indicating that 25(OH)D concentrations do not decrease dramatically in populations who temporarily reside in Canada but go back to their countries of origin during the Canadian winter. This study did not find a statistical relationship between low levels of vitamin D and LTBI which suggests that in the presence of overall good health, lower than ideal levels of 2S(OH)D, may still be exerting a protective immunological effect against LTBI reactivation. The challenge remains to determine a critical 2S(OH)D concentration at which reactivation is more likely to occur.

Stereoselective synthesis of 5-substituted pyrrolo[1,2-c]imidazol-3-ones. Access to aldosterone synthase inhibitors and chiral precatalysts

Compounds containing the pyrrolidine moiety are key substructures of compounds with biological activity and organocatalysts. In particular, annulated chiral pyrrolidines with alpha stereogenic centers have aldostereone synthase inhibition activity. In addition, 5-substituted pyrroloimidazol(in)ium salts precursors to N-heterocyclic carbene (NHC) precatalysts are rare due to a lack of convenient synthetic routes to access them. In this thesis is described a rapid synthesis of NHC precursors and a possible route to 5-substituted pyrroloimidazole biologically active compounds. The method involves the preparation of chiral saturated and achiral unsaturated pyrrolo[I,2- c]imidazol-3-ones from N-Cbz-protected t-Butyl proline carboxamide. The resulting starting materials may be used to prepare the target chiral annulated imidazol(in)ium products by a two-step sequence involving first stereoselective lithiation-substitution, followed by POCh induced salt formation.

Diastereoselective Lithiation-Substitution of N-Silyl-Protected-(S)-Tetrahydro-1H-pyrrolo[1,2-c]imidazole-3(2H)-ones and Applications of Their Derivatives

This thesis describes a method involving the preparation of an L-proline-derived imidazolone protected with an N-triethylsilyl group that undergoes diastereoselective lithiation followed by electrophile quench to give C5-substituted products with syn stereochemistry. The N-silylated derivatives may be more easily N-deprotected as compared to previous N-t-Bu analogues to give secondary ureas. These may serve as precursors to N-phenyl chiral bicyclic guanidines or as NHC precursors for synthesis of corresponding complexes.