Abstract
ABSTRACT This thesis consists of two parts Part I, gives a brief introduction of Diels-Alder reactions and masked o-benzoquinones and contains the results and discussion along with the experimental section of the novel domino retro-Diels-Alder (rDA) – Diels-Alder (DA) protocol applied to the masked o-benzoquinone chemistry for the synthesis of several bicyclo[2.2.2]octenones and bicyclo[2.2.2]octadienones. This procedure is focused on 3 main objectives: 1) utilization of a masked o-benzoquinone dimer which was a side product in the masked o-benzoquinone Diels-Alder chemistry; 2) increase the yield of the Diels-Alder adducts which were difficult or not possible to synthesize by earlier procedures; 3) decrease the number of synthetic steps to achieve the desired Diels-Alder adducts which previously needed more steps. Part II, gives a brief introduction of diabetes and peroxisome proliferator activated receptors (PPARs) and the “Design, Synthesis and In Vitro Studies of Novel PPAR Agonists as Anti-Diabetic Agents” and includes the experimental section of the present work. A knowledge based drug design is used for synthesizing these novel ligands. After successfully preparing several molecules, bioassay was conducted and IC50 [using Scintillation Proximity Assay (SPA)] and EC50 [using Transcriptional Activation Assay (TA)] were obtained for all the compounds. Compound 6e was identified to be potent PPARα,γ dual agonist and is presently under in vivo studies (KKAy mice models).