The Use of Organometallic Reaction in the Syntheses of Anticancer Agents.( I )

Increasing attention is currently draw to the development of organopalladium and organocopper reagents, due to their ability to build up specific C(sp2)-C(sp/sp2) and C(sp2)-N(amine/amide) bonds. Several organometal-catalyzed reactions have been developed, such as Suzuki arylation, Sonogashira alkynylation, Buchwald-Hartwig amination, Ullmann reaction, Chan-Lam reaction and so on. In the new drug development, the use of organopalladium and organocopper reagents is helpful increase the connectivity between core structure and pharmacophore, increase the diversity of structure, and benefit the enhancement of success rate of small molec drug development. The biological result indicated that the preliminarily synthesized six compounds show significant antiproliferative activity against lung A549 and colorectal HCT116 cancer cells. As a result, this project is attempted to extend the preliminary result and to undergo structural optimization. In order to develop potent anticancer agents with structural novelty, this project plans to use organopalladium and organocopper catalysts to synthesize six classes of compounds: indolylalkylamine, indol-3-yl carboxamide, 2-pyridone, 3-substituted uracil, partially hydrogenated heteroaryl-2-hydroxybenzamides, and 2-aryl-ethenylcarbonyl derivatives.