Design And Synthesis Of Novel PPARγ Agonist

The status of insulin sensitizer was introduced and studied. Total synthesis of the thiazolidinedione class of insulin-sensitizer rosiglitazone was studied. Rosiglitazone was synthesized simply and efficiently from 2-Chloropydine and 2-(Methyl amino)ethanol through 4 steps. The Willimson reaction condition of 4- [2-(Methyl-pyridin-2-yl-amino) -ethoxy] -benzaldehyde (2) was optimized, and a simple and rapid method to purify it was obtained. Catalytic hydrogenation reaction system of 5-{ 4- [2- (Methyl-pyridin-2-yl-amino) -ethoxy] benzylidene } -thiazolidine-2, 4 - dione (3) was optimized and the total yield was 21.6%. The results show that the facile synthetic scheme has the characteristic of mild reaction condition, high yield and was simple to operate.Based on the synthesis method and the function of decreasing blood glucose levels of rosiglitazone, and the report on benzoquinones which resulted in a significant decrease in blood glucose levels, a novel non-thiazolidinedione class of PPARy agonist 2, 5-Dihydroxy-3- {4-[2- (methyl- pyridin-2- yl-amino) - ethoxy] -phenyl}-6-phenyl-[l, 4] benzoquinone (4) was designed and synthesized. The method to purify compound 4 was resolved. A novel method to prepare the intermediate from phenylacetyl chloride was selected in this paper. The facile synthetic scheme put forward in this work is simple to operate and has the characteristic of high yield and good feasibility.