Double Allylation Reaction Of Pyridines And The Synthesis Of Spiro-indolinone MDM2 Antagonist

There are two parts in this paper. The first part we introduced the Grignard reagent promoted the double allylation reaction of pyridines. The second relateds to the synthesis of spiro-indolinone MDM2 antagonist.1. Pyridine derivatives are widely used in functional material, pharmaceutical,rubbe, insecticide and additive, it is one of the most important in organic chemistry containing heterocyclic compound. Currently, Allyl derivatives of pyridine and it`s synthetic method has been reported rarely. We discovere Grignard reagent can promote allylation reaction of bromopyridine and allyl chloride, then we can get diallyl-substituted and single-allyl-substituted product. The deprotonation of Grignard reagent with single-allyl-substituted product can also produce diallyl-substituted product, also this method was characterized with high efficiency and good functional group tolerance.2. For widespread malignant disease, researchers have found a variety of anticancer drugs, In recent years, scientists have found a new novel scaffold,which is Spiro-indole ketones. These drugs can inhibit P53-MDM2 protein binding, thereby inhibiting the growth of tumor cells. Based on the literature and previous studies, We synthesized some spiro-indole ketones based on the method of [3+2] cycloaddition reaction. Then we optimized the structure of the anti-tumor compound RO8994, We reserved the spiro indolinone structure of the original compound,changed the original fat-soluble molecules tert-butyl alkyl chain into a rich charge of olefin compound to give a series of derivatives, and we will conduct a new round of biological activity test, but the test is still in progress.