New 3,3-disubstituted oxetanes and azetidines: Synthesis, evaluation and new opportunities for drug discovery

3,3-Disubstituted oxetanes and azetidines are valuable motifs with attractive physichochemical properties and are potential replacement groups for gem-dimethyl, carbonyls and larger heterocycles. The development of robust methods to access such scaffolds is highly desirable. In this thesis, novel 3,3-disubstituted oxetanes and azetidines are prepared through the in situ generation of carbocations and radicals. The suitability of these new motifs for drug discovery programmes is also evaluated. In this regard, 3,3-diaryloxetanes are first assessed as replacement groups for diarylketones and 1,1-diarylalkanes in part 3. These oxetanes are synthesised through a Friedel–Crafts reaction with oxetanols. The comparison of the physicochemical properties between 3,3-diaryloxetanes, benzophenones and 1,1-diarylalkanes shows that these oxetanes are suitable replacements groups for medicinal chemistry application. The preparation of new 3,3-diarylazetidines and 3-arylsulfanyl-azetidines is then described in part 4. This was achieved through in situ generation of azetidinyl carbocations from NCbz-azetidin-3-ols using Ca and Fe catalysts. These carbocations can react with nucleophiles such as (hetero)aromatics and thiols giving new azetidine scaffolds in high yields. The generation of oxetanyl and azetidinyl carbocations required the alcohol precursors to bear electron-rich aromatics. An alternative Fe-catalysed Friedel–Crafts reaction is then described in part 5, where the use of hexafluoroisopropanol as solvent enables oxetanyl carbocation formation from oxetanols bearing phenyl and electron-poor aromatics. Previously inaccessible 3,3-diaryloxetanes are synthesised as well as one example of 3,3-diarylazetidine and 3-arylsulfanyl-oxetane. New oxetane and azetidine scaffolds are then prepared through in situ generation of radicals in part 6. This was achieved through photoredox-catalysed decarboxylation of oxetane and azetidine carboxylic acid precursors. The radicals are trapped with alkenes to give new 3-aryl-3-alkyl oxetanes and azetidines. A two-step protocol is also described to efficiently access the acid precursors. This involves the preparation of 3-aryl-3-furanyl intermediates through Friedel–Crafts reaction followed by oxidative cleavage of the furan.Open Acces

Evaluation of a Large Eddy Simulation's Applicability to a Worst Case Fire Scenario

The applicability of a large eddy simulation to a small scale turbulent flow problem is assessed by comparing modeled results to those recovered from a physical apparatus with the same geometry. The computational domain is that of a rearward facing step with a channel-width to step aspect ratio of2:1. The code utilized is LES-3d, and focus is placed on measuring the discrepancy between the recovered recirculation zone lengths when initial and boundary conditions of the virtual flow and duct are altered. It is found that the modeled results exceed the experimental by a factor of 2. These preliminary results point to the degree to which the user-specified parameters of upstream boundary conditions, inlet length, flow speed, flow profile, and computational domain resolution characterize and affect the simulated flow behavior. LES-3d's treatment of these crucial parameters is tested by performing additional experiments in a constant cross section straight duct with the same dimensions as the inlet to the previously mentioned rearward facing step. After looking into LES-3d's set of assumptions and means of incorporating the user's simulation preferences, a second set of simulations are executed with what are considered the optimal settings to guarantee the greatest degree of convergence between the experimental and modeled results. Findings indicate almost a 25% improvement in the recirculation zone measurements; however, other flow parameters such as the profile and boundary layer thickness are not maintained.This report serves as the computational portion of an ongoing study aimed at engineering a bench-scale apparatus to test the effectiveness of non-halogenated fire suppression agents in aircraft engines. The work is performed in cooperation with the National Institute of Standards and Technology, Gaithersburg, MD and the University of Maryland, College Park, MD

Assessment of the physiological and biochemical characterization of a Lactic acid bacterium isolated from chicken faeces in sahelian region

The aim of this work was the examination of the microbiological and technological properties of a lactic acid bacterium (CWBI-B623) isolated from chicken faeces in sahelian region (Burkina Faso). The strain CWBI-B623 is a Gram positive rod, asporogenous, catalase-positive, facultatively anaerobic, non motile and mesophilic. The analysis showed that it produce L(+)-lactic acid via homofermentative pathway and it was able to ferment an important number of the carbohydrates of API 50CHL system. The 16S-rDNAsequence analysis revealed that the isolate was phylogenetically a member of the genus Lactobacillus and formed a subline within the Lactobacillus casei cluster. The minimal inhibitory concentration of CWBI-B623 for bile salts was higher than 1% and the survival rates to acidity with pH 3.0 and pH 2.5 were 26 and 1.2%, respectively. CWBI-B623 is an Lactobacillus casei species based on its physiological and biochemical properties and it could be a good candidate for probiotic formulations.Key words: Lactic acid bacteria, Lactobacillus, probiotic, biodiversity