Lycorane 及其类似物的全合成 及铱催化不对称烯丙基烷基化研究

	Lycorane 及其类似物的全合成及铱催化不对称烯丙基烷基化研究; Total Synthesis of Lycorane and Its Analogs and Iridium Catalyzed Asymmetric Allylic Alkylation
	章天元
导师	杨玉荣
摘要	This dissertation describes the total synthetic study of the alkaloids (+)-α-lycorane, (+)-trans-Dihydrolycoricidine, (+)-7-deoxypancratistatin and the iridium-catalyzed allylic alkylation reaction of asymmetric branched alkyl substitutions, including the following two chapters. In chapter 1, the total synthetic study of the alkaloids (+)-α-lycorane, (+)-transDihydrolycoricidine, (+)-7-deoxypancratistatin of the Amaryllidaceae Alkaloids is presented ， Firstly, the progress of the total synthesis of (+)-α-lycorane and (+)-trans-Dihydrolycoricidine is reviewed in recent years; Lycorane alkaloid (+)-α-lycorane contains a pyrrolophenanthridine tetracyclic (Galanthan ring) structure and three consecutive chiral centers; The dual Ir/amine catalytic allylation reaction developed by Carreira's group as the key reaction is employed to construct the two chiral centers embed in target natural product. The final chiral construction could be achieved by the induction of neighboring chirality, The endgame of (+)-α-lycorane is achieved in 13 steps with an overall yield of 11.9%. (+)-trans-Dihydrolycoricidine which displays good anti-tumor and antiviral activity, has a six-membered amino cyclic alcohol structure with five consecutive chiral centers. The double bond of the advanced intermediate β,γ-unsaturated ketone during the synthesis of (+)-α-lycorane is easily migrated under alkaline conditions to obtain α,β-unsaturated ketone. Subsequently, α,β-unsaturated ketone is successfully constructed by stereoselective reduction, epoxidation reaction and epoxy ring-opening reaction to build continuous chiral centers on the six-membered aminocyclic alcohol, and then the synthesis of the target molecule can be achieved by several chemical transformations in a total of 12 steps with an overall yield of 7.2%. The synthesis of (+)-7-deoxypancratistatin was also underexplored. In chapter 2, the iridium-catalyzed allylic alkylation reaction with asymmetric branched chain alkyl substitution is introduced. The progress of iridium-catalyzedAbstract III allylic alkylation research is reviewed in the last 20 years. After extensive experiments, a catalytic system suitable for the reaction of branched alkyl substituted allyl with malonate is found. The optimal reaction is performed with (R)-Ir-Tol-BINAP as a catalyst developed by Krische group and easily prepared leaving group (-OAc) in elevated temperature. Using optimized conditions, 15 alkyl-substituted allyl substrates with better yields, enantioselectivity and perfect regioselectivity were obtained. This catalytic system paves the way for new carbon-carbon construction, and it is expected that asymmetric allylic alkylation can be applied to the total synthesis of complex natural products.
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74495
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	章天元. Lycorane 及其类似物的全合成及铱催化不对称烯丙基烷基化研究, Total Synthesis of Lycorane and Its Analogs and Iridium Catalyzed Asymmetric Allylic Alkylation[D],2021.

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