The selective manipulation of hydroxyl groups in di- and polyols is a frequently encountered problem in organic synthesis. Such processes are often tedious and/or moderate yielding, and often necessitate multistep protection / deprotection sequences. Applying boron–diol interactions previously exploited in molecular recognition and based on methods previously developed in our research group, we have developed two classes of chemical transformations: 1. Regioselective sulfonylations of carbohydrate derivatives catalyzed by a borinic ester, providing access to the corresponding mono-tosylates in high yields; 2. Selective monoalkylations and monosulfonylations of structurally diverse 1,2- and 1,3-diol substrates.

The selective manipulation of hydroxyl groups in di- and polyols is a frequently encountered problem in organic synthesis. Such processes are often tedious and/or moderate yielding, and often necessitate multistep protection / deprotection sequences. Applying boron–diol interactions previously exploited in molecular recognition and based on methods previously developed in our research group, we have developed two classes of chemical transformations: 1. Regioselective sulfonylations of carbohydrate derivatives catalyzed by a borinic ester, providing access to the corresponding mono-tosylates in high yields; 2. Selective monoalkylations and monosulfonylations of structurally diverse 1,2- and 1,3-diol substrates.

It is well known that boronic acids can bind with diols and can be further applied as chemosensors for biomolecules such as carbohydrates and dopamine. Carbohydrates are known to mediate a large number of biological and pathological events. Small and macromolecules capable of carbohydrate recognition have great potentials as research tools, diagnostics, vectors for targeted delivery of therapeutic and imaging agents, and therapeutic agents.

Protected DHA units, known as dioxanones, are interesting compound which can be used as the building blocks for synthesis of polyoxygenated natural products. The direct aldol reaction is employed for converting of those inexpensive starting materials into enantioenriched products of complexed structures. The stereocontrol in the first aldol reaction is achieved by using organocatalysis. Second aldol reaction is conducted by lithium enolate chemistry leading to anticisanti aldols as a major isomer. On the other hand boron chemistry provides antitransanti products. This strategy is used for synthesis of higher sugars.

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The purpose of this study was to examine if the addition of protein to a carbohydrate supplement (CHO+PRO), provided during a simulated soccer match, would reduce fatigue and muscle glycogen utilization in comparison to an isocaloric carbohydrate only supplement (CHO). Two female and eight male (n = 10) trained soccer players performed a modified version of the Loughborough Intermittent Shuttle Test (LIST) on two separate occasions, followed by a run to exhaustion (RTE). Supplements were provided 10 minutes before the simulated match and at the beginning of half-time, but not during exercise in order to create real-match conditions. Supplements were composed of 2.8% protein + 7% carbohydrate (CHO+PRO) or 9.8% carbohydrate (CHO). Muscle biopsies were performed before and at the end of the LIST, after which iv participants ran to exhaustion. No differences were found between treatments for RTE (489 ± 121 sec for CHO and 589 ± 186 sec for CHO+PRO) or glycogen utilization (37.9 ± 7.6 µmol•g wet wt-1 during the CHO and 29.1 ± 6.0 µmol•g wet wt-1 during the CHO+PRO). No differences were found for the other measurements such as sprint times, heart rate, RPE, blood glucose, lactate, and insulin. Blood Creatine kinase (CK), and overall muscle soreness were measured 24 hours after each trial in order to evaluate muscle damage but no differences between treatments were found. In accordance with these findings, the phosphorylation state of the protein FOXO3a was not altered differently by the treatments. These results suggest that the addition of protein to a traditional carbohydrate-only supplement provided immediately prior to and at the half of a simulated soccer match does not further improve the benefits of a CHO supplement. / text

The oligosaccharide domain of many secondary metabolites have been demonstrated to be pivotal for the biological efficacy of the parent glycoconjugate. In most cases, the alteration or removal of these carbohydrate residues results in the greatly diminished or completely abolished biological activity of the natural product. A common structural motif found in secondary metabolites possessing carbohydrate domains is the 2-deoxy-β-glycosidic linkage which are among the most difficult to establish in a stereocontrolled fashion. Chapter I provides background information describing the difficulties associated with the synthesis of 2-deoxy-β-glycosidic linkages in addition to a sampling of the current methodology available for their construction. Chapter II details our use of diethyl and pinacol phosphite glycosyl donors towards a direct synthesis of a designed 2-deoxy-β-oligosaccharide in a "one-pot" process which constitutes a novel approach towards the synthesis of these glycosidic linkages. Lomaiviticin A was isolated as the major metabolite from fermentation of the halophilic strain LL-37I366 which was later assigned the name Micromonospora lomaivitiensis. Lomaiviticin A displayed potent biological activity towards numerous cancer cell lines with IC50 values ranging from 0.01 to 98 ng/ml. While postulated to induce double-stranded DNA cleavage, the mechanism of action was unique when compared to known DNA-damaging agents such as adriamycin and mitomycin C. Chapter III details progress towards the synthesis of lomaiviticinone employing an "inside-out" strategy to take advantage of the molecule's own C2-symmetrical nature. The focus of the chapter will pertain to our efforts to construct the stereochemically-rich cyclohexenone central core highlighted by the use of organometallic C-C bond formation processes.

Obesity is the most prevalent nutritional disorder in cats (Felis catus; Hoenig et al., 2011). High carbohydrate diets, prescribed for weight loss, may contribute to adiposity (Thiess et al., 2004). The effects of a high fat (HF; 30% fat, 10% carbohydrate), high carbohydrate (HC; 10% fat, 46% carbohydrate) and a moderate diet (15% fat, 30% carbohydrate) supplemented with a calorie restriction mimetic (mannoheptulose (MH); 8 mg/kg BW), fed to energy requirements, on feline metabolism and behaviour were investigated (n=20; 4 ± 2.5 kg). An 11 week acclimation procedure was designed to adapt cats to 24-hr restriction within a chamber used for indirect calorimetry. Stress indicative behaviour (Kessler and Turner, 1997) declined with repreated exposure to increasing lengths of restriction within chambers and on week 11 stress levels were low and consistent (P<0.05). Neither the HF nor HC diet impacted body weight (p>0.05); however, HF feeding caused an increase in body fat (0.75 kg (baseline) vs. 1 kg (86d)) after long-term feeding. Energy expenditure (EE) was not impacted by dietary fat/carbohydrate. Respiratory quotients (RQ) increased and decreased with exposure to the HC (fasted= 0.80 ± 0.008; fed= 0.87 ± 0.008), HF (fasted= 0.76 ± 0.008; fed= 0.78 ± 0.008) diet, respectively. Glucose to insulin (G:I) ratio increased with HF feeding; indicating improved insulin sensitivity. Physical activity, measured using accelerometers, declined with HF (-1.6 counts/hr) and HC (-2.8 counts/hr) feeding from baseline. T-maze performance decreased and increased with HF (-0.85 score/10) and HC (0.85 score/10) feeding from baseline (p<0.05). MH did not impact body weight or composition (p>0.05). Area under the curve for EE increased during the 15-22 hour post feeding with MH treatment (2370.3 (-MH) vs. 3292.0 (+MH) ± 0.0002). RQ and G:I were not impacted by MH (p>0.05). MH increased play motivation, measured using obstruction tests (p<0.05). Diets high in carbohydrate are not ideal for weight loss since they negatively impact insulin sensitivity and voluntary EE. Diets promoting elevated EE, activity and normal glucose/insulin profiles are ideal for weight control and MH offers a unique opportunity for use in weight loss regimes. / This work was funded by Procter and Gamble Co.

Clostridium difficile is a Gram-positive bacterium that is the most common cause of hospital-associated and antimicrobial-associated diarrhea in humans. Monteiro and co-workers have discovered that C. difficile expresses three cell-surface polysaccharides, named PS-I, PS-II and PS-III. Interestingly, PS-I was determined to be present in a ribotype 027 strain, the ribotype responsible for recent deadly outbreaks worldwide. In this work, the total chemical synthesis of the PS-I pentasaccharide with a linker molecule by a linear synthesis strategy from four monosaccharide building blocks is described: α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-α-D-Glcp-(1→2)-α-D-Glcp-(1→O(CH2)5NH2 3 ↑ 1 α-L-Rhap The synthesized PS-I pentasaccharide will be conjugated to a protein carrier for evaluation as an anti-C. difficile glycoconjugate vaccine.

The cell membrane is a complex structure with many functions that can affect cellular processes. For this reason, a model possessing characteristics similar to those of the natural cell membrane is required for the investigation of various functions and properties belonging to this important structure. Presented is the synthesis of a glycolipid analogue possessing both a C-4’ thiol functionalization (for binding to an Au(111) electrode) and an anomeric triazole-linked phytanyl chain (for integration into a phospholipid bilayer). Additionally, a similar analogue without thiol functionalization was synthesized for use as a dilution molecule to prevent aggregation of the tether analogue during monolayer assembly. Aqueous compartments will exist above and below the bilayer allowing for future integration and functional analysis of membrane proteins. Glycosylation at the anomeric position of a lactosyl donor with propargyl alcohol gave a propargyl lactoside that underwent several steps of selective protection to give access at O-4’ for triflation. Displacement of the triflate gave a thioacetate functionalized disaccharide. Both the propargyl lactoside and the thioacetate functionalized disaccharide underwent copper-catalyzed azide-alkyne cycloadditions with phytanyl azide. Subsequent deprotections gave two novel glycolipid analogues. / NSERC