The Application Research Of Decarboxylation Michael Addition-Redox Aromatization In The Syntheis Of Histone Deacetylase Inhibitors

Histone deacetylase inhibitors can inhibit histone deacetylases' activity, promote non-histone and histone acetylation, which effectively inhibit tumor cell growth. The structure of HDACi generally include three parts:zinc ion binding, linker, surface recongnition. The paper aims to synthesize a series polycyclic compounds as the surface recongnition of HDACi to improve its activity.The paper, using o-bromo benzaldehyde analogues as the starting material, synthesizes 10 2--formyl- phenylpropenoic acid analogues via Heck reaction. Then,these compounds react with trans-4-hydroxy-L-proline in the optimal conditions to get 10 2H-pyrrolo [1,2-b] isoquinoline compounds,4 2H-indole [1,2-b] isoquinoline compounds via self-redox amination-Michael addition-decarboxylation aromatization. And the synthesis of 14 polycyclic aromatic compounds have not been reported.In addition, this paper also studied the use of oxidation- decarboxylation-aromatization in synthesis of N-alkyl-1H-pyrrole compounds throung two experimental methods:step-by-step oxidation and one pot oxidation. The used oxidation system as below: toluene is as solvent, CuBr as catalyst, DTBP as oxidant, TEMED/Et3N as ligand, react on 110℃for 12h. Using this method, we get 4 N-alkyl-1H-pyrrole compounds.