No description available.

No description available.

A new class of oxazolidinone chiral auxiliary has been synthesized from various α-amino acids, incorporating a perfluoroalkyl functional chain as a soluble support. This feature allows the chiral auxiliaries to be employed under standard solution-phase reaction conditions, and rapidly purified from crude mixtures using fluorous solid phase extraction (FSPE). Our investigation of these new materials has been divided into two main sections. To obtain the chiral auxiliaries in multi-gram quantities a synthetic protocol was designed, where efficiency and reproducibility were the primary objectives. Meeting these goals required an extensive study of the reactivity of perfluoroalkyl nucleophiles. This study identified a versatile and scalable protocol for the perfluoroalkylation of the required amino acid starting materials. These results have allowed us to design a general, five-step synthetic pathway to create the fluorous chiral auxiliaries quickly and effectively. The new auxiliaries were then applied in several model reactions, specifically chosen to examine the reactivity and behavior of these compounds. In particular, the auxiliaries were tested for their stereoselectivity, recyclability, and ease of purification, in a series of Aldol reactions, 1,3 dipolar cycloadditions, and radical conjugate additions. This set of model reactions, combined with the facile and efficient synthesis clearly demonstrates that these new chiral auxiliaries are useful alternatives to the non-fluorous oxazolidinone chiral auxiliaries currently employed in stoichiometric asymmetric syntheses. / February 2006

A new class of oxazolidinone chiral auxiliary has been synthesized from various α-amino acids, incorporating a perfluoroalkyl functional chain as a soluble support. This feature allows the chiral auxiliaries to be employed under standard solution-phase reaction conditions, and rapidly purified from crude mixtures using fluorous solid phase extraction (FSPE). Our investigation of these new materials has been divided into two main sections. To obtain the chiral auxiliaries in multi-gram quantities a synthetic protocol was designed, where efficiency and reproducibility were the primary objectives. Meeting these goals required an extensive study of the reactivity of perfluoroalkyl nucleophiles. This study identified a versatile and scalable protocol for the perfluoroalkylation of the required amino acid starting materials. These results have allowed us to design a general, five-step synthetic pathway to create the fluorous chiral auxiliaries quickly and effectively. The new auxiliaries were then applied in several model reactions, specifically chosen to examine the reactivity and behavior of these compounds. In particular, the auxiliaries were tested for their stereoselectivity, recyclability, and ease of purification, in a series of Aldol reactions, 1,3 dipolar cycloadditions, and radical conjugate additions. This set of model reactions, combined with the facile and efficient synthesis clearly demonstrates that these new chiral auxiliaries are useful alternatives to the non-fluorous oxazolidinone chiral auxiliaries currently employed in stoichiometric asymmetric syntheses.

A new class of oxazolidinone chiral auxiliary has been synthesized from various α-amino acids, incorporating a perfluoroalkyl functional chain as a soluble support. This feature allows the chiral auxiliaries to be employed under standard solution-phase reaction conditions, and rapidly purified from crude mixtures using fluorous solid phase extraction (FSPE). Our investigation of these new materials has been divided into two main sections. To obtain the chiral auxiliaries in multi-gram quantities a synthetic protocol was designed, where efficiency and reproducibility were the primary objectives. Meeting these goals required an extensive study of the reactivity of perfluoroalkyl nucleophiles. This study identified a versatile and scalable protocol for the perfluoroalkylation of the required amino acid starting materials. These results have allowed us to design a general, five-step synthetic pathway to create the fluorous chiral auxiliaries quickly and effectively. The new auxiliaries were then applied in several model reactions, specifically chosen to examine the reactivity and behavior of these compounds. In particular, the auxiliaries were tested for their stereoselectivity, recyclability, and ease of purification, in a series of Aldol reactions, 1,3 dipolar cycloadditions, and radical conjugate additions. This set of model reactions, combined with the facile and efficient synthesis clearly demonstrates that these new chiral auxiliaries are useful alternatives to the non-fluorous oxazolidinone chiral auxiliaries currently employed in stoichiometric asymmetric syntheses.

No description available.

No description available.

No description available.

Une réaction simple de condensation de l'acide thiocyanique avec un cétohexose peut conduire à la formation d’une dizaine de 10 oxazolidinethiones (OZTs) ou oxazolinethiones (OXTs) distinctes. La question que nous nous sommes posée a été “comment gérer une chimie aussi complexe?” Un contrôle attentif des conditions de réaction, associé à des séquences de purification comportant des protections sélectives et diverses fonctionnalisations, peuvent certainement être utiles. Un jeu chimique subtil et stimulant a été développé entre des pré- et post-protections sélectives et des réactions originales de fonctionnalisation. Dans ce travail de thèse, nous avons mis à l’étude de nouvelles tactiques de synthèse et de purification pour accéder à des OZTs et des oxazolidinones (OZOs) ancrées sur des charpentes des cétohexoses. Ces travaux ont été mis en application notamment en série D-fructo et dans les séries épimères D-psico et D-tagato dont la chimie ont été peu explorée en comparaison d’autres séries monosaccharidiques. Nous avons ainsi mieux maîtrisé les approches chimiques permettant d’accéder à ces thionocarbamates saccharidiques et ainsi de valoriser ces molécules dont l’intérêt d’un point de vue biologique et chimique est important. Dans ces études, nous avons élaboré une bibliothèque de formes tautomères fixes de composés hybrides qui ont été soumis à des essais biologiques. Ainsi, ce groupe de composés a fait l’objet de tests antimicrobiens, livrant des résultats très intéressants. Par ailleurs, les meilleurs inhibiteurs de GLUT5 seront utilisés dans le développement de nouveaux outils biochimiques pour une meilleure compréhension des rôles joués par ce transporteur du D-fructose en relation au le diabète de type 2 et de l'obésité. / A simple condensation reaction of thiocyanic acid with a ketohexose can provide a library of up to 10 different molecules composed of oxazolidinethiones (OZTs) or oxazolinethiones (OXTs). The question arising is “how to manage such a complex chemistry?” Careful control of the reaction conditions associated with purification sequences (involving selective protection or functionalization) can certainly help. A subtle and challenging chemical game could be played between selective pre- and post-protections and original functionalizing reactions. In this PhD work, we disclose the development of new chemical and purification tactics to access OZTs and oxazolidinones (OZOs) anchored onto ketohexose scaffolds, namely D-fructo and its epimers D-psico, D-tagato, whose chemistry has been poorly investigated in comparison with other monosaccharidic systems. Furthermore we have improved our understanding about saccharidic thionocarbamates chemistry for a better valorization from both chemical and biological point of view. We have generated a library of fixed tautomeric forms of hybrid compounds to be submitted to biological tests. This panel of compounds was subjected to antimicrobial screening and some molecules have shown very efficient effects. Moreover, the leading inhibitors of GLUT5 will be used in the development of biochemical tools for a better comprehension of the role of this D-fructose transporter in relation to type 2 diabetes and obesity.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.