Poly(ADP-ribose) polymerase (PARP) represents a large family of enzymes that are activated upon DNA breakage, which are then involved in a cascade of reactions that eventually lead to cell death. PARPs, known to cause a variety of damage to the human body, are targets of many researches’ investigating potential inhibition mechanisms. To this point, plenty of PARP inhibitors have been synthesized and tested for potency against many diseases. Some have great potency against particular diseases, while others are already being used as drugs. The current research suggests a potential synthesis of novel PARP inhibitors, to be accomplished through Diels-Alder chemistry. The proposed compounds consist of an isoindolinone core bearing different functional groups. Three different strategies are described for the synthesis of the novel PARP inhibitors and all protocols involve sulfur dioxide extrusion chemistry to create a diene, the desired transient starting material. The diene is envisioned further to be reacted with a variety of dienophiles to give possibly potential PARP inhibitors. / NSERC

No description available.

No description available.

The synthesis of methyl 3,6-dimethylpyridine-2-carboxylate (192) by the Diels-Alder addition of 3-butene-2-one dimethylhydrazone (190) and methyl-2-butynoate (16) is described. The structure of 192 was confirmed by the synthesis of methyl 2,6-dimethylpyridine-3-carboxylate (195), the opposite regioisomer.The synthesis of methyl 3,5-dimethylpyridine-2-carboxylate (199) from [4+2] cycloaddition of 2-methyl-2-propenal dimethylhydrazone (171) and 16 is described. In addition to producing a small amount of 199 directly, the reaction produced an intermediate of possible structure 198 which yielded 199 on catalytic dehydrogenation.On prolonged heating, 2-acetyl-5-methylpyridine (200) was produced by the reaction of diene 171 with methyl vinyl ketone (176).The preparation of 2-cyan-5-methylpyridine (201) from the tetrahydropyridine derivative 175 via catalytic dehydrogenation is described.The synthesis of 5,7-dioxo-3-methyl-6-phenyl-1,1.,5,6,7-pentahydropyrroloC3,1.-b] pyridine (202) through the Diels-Alder addition of diene 171 and N-phenylmaleimide (149) is described. Also reported is the preparation of 5,7-dioxo-3-methyl-6-phenyl-3,5,6-trihydropyrrolo [3,1+-b]pyridine (203) via dehydrogenation of 202. / Department of Chemistry

No description available.

No description available.

No description available.

Thèses (Ph.D.)--Université de Sherbrooke (Canada), 2001. / Titre de l'écran-titre (visionné le 20 juin 2006). Publié aussi en version papier.

Thèses (M.Sc.)--Université de Sherbrooke (Canada), 1998. / Titre de l'écran-titre (visionné le 24 août 2006). Publié aussi en version papier.

Thesis (docteur ès sciences)--Université de Genève. / "Thèse No 2144." Includes bibliographical references (p. [136-139]).