Synthesis Of THPs From MBH Carbonates,Studys Towards Hydroxalkoxylation/Claisen Reactions And The Synthesis Of Cortistatin A

This thesis includes a one-pot synthesis of tetrahydropyridines derivatives from Morita-Baylis-Hillman carbonates,studys towards Br?nsted acid-catalyzed hydrox-alkoxylation/Claisen rearrangement sequence to provideγ,δ-unsaturated ketones and studys on the synthesis of Cortistatin A.In chapter 1:A one-pot synthesis of tetrahydropyridines derivatives from Morita-Baylis-Hillman carbonatesTetrahydropyridines are one of the most important nitrogen-containing heterocyclic materials,which are widely used in biological medicine,material science,chemical industry and so on.We have designed a novel approach to construct tetrahydropyridines via three-component formal[3+2+1]annulation.Ethyl acetoacetate react with MBH carbonates to deliver functionalized acetoacetate intermediate through allyl alkylation reaction,then the intermediate would be further converted into multisubstituted tetrahydropyridines through an Imine/Michael condensation in the presence of a primary amine.Experiment results prove that this protocol is a convenient method for preparation of tetrahydropyridines with functionality tolerance and excellent reaction efficiency.In chapter 2:Studys towards Br?nsted acid-catalyzed hydroxalkoxylation/Claisen rearrangement sequence to provideγ,δ-unsaturated ketones.Claisen rearrangement is a classic reaction which was discovered in the 20th century.Over more than 100 years of development,the reaction has presented commendable application prospects.we have developmented a facile synthesis ofγ,δ-unsaturated ketones through Br?nsted acid-catalyzed hydroxalkoxylation/Claisen rearrangement sequence.In the initial step,Br?nsted acid-catalyzed intermolecular hydroalkoxylation of ethynylaniline derivative with allylic alcohol to generate allyl vinyl ethers has taken place,afterwards,the allyl vinyl ethers undergo Claisen rearrangement.We have found that conjugated dien-ketone would be obtained if allylic alcohol was replaced with propargyl alcohol by screening substituents.In chapter 3:Studys on the synthesis of Cortistatin A.Cortistatin A,isolated from a marine sponge,Corticulum simplex,by Kobayashi in 2006exhibit highly selective antiproliferative activity against human umbilical vein endothelial cells（HUVEC）(IC₅₀=1.8 nM).Therefore,it is very important to carry on research work about the total synthesis of Cortistatin A.We have designed three ways to synthesize its core skeleton on the basis of existing reports.1)Samarium（I1）Iodide promoted cyclization of keto and olefins;2)free radical cyclization of aryl radical and olefins;3)intramolecular RCM cyclization.Finally,we obtained the ABCD-tetracyclic core skeleton of Cortistatin A by using the third strategy.