生物碱 quinocarcinamide 和 didehydroparvistemonine 关键前体的合成

	生物碱 quinocarcinamide 和 didehydroparvistemonine 关键前体的合成
	石莉
导师	韦堃
关键词	Ir 催化不对称烯丙基胺化、Ir/胺双元催化、(+)-quinocarcinamide、 didehydroparvistemonine Keywords: Ir-catalysis asymmetric allylamination, Ir/amine dual catalysis, (+)-quinocarcinamide, didehydroparvistemonine
摘要	本论文围绕过渡金属 Ir 催化不对称烯丙基化反应开展了 quinocarcinamide 前体和脱氢细花百部碱 didehydroparvistemonine 前体的不对称合成研究。主要包含以下两章。第 1 章首先简述了四氢异喹啉生物碱 quinocarcin 的化学合成研究。其次重点展开我们的研究工作：利用过渡金属 Ir 催化不对称烯丙基胺化反应作为关键反应高效构建了第一个关键手性中心，产物经臭氧化切断双键并还原得到相应的一级醇产物，经 X-ray 单晶结构分析验证了不对称烯丙基胺化产物的绝对构型。并以此切入，依次通过 Stille 偶联反应、交叉烯烃复分解反应得到取代的烯丙基溴化物。该溴化物在叔丁醇钾的作用下以高度立体选择性的 SN2′反应得到 1,3- cis-二取代的四氢异喹啉环，完成了(+)-quinocarcinamide 关键四氢异喹啉环的手性合成，并最终合作完成了(+)-quinocarcinamide 的首次不对称合成。第 2 章阐述了我们课题组关于细花百部碱的部分合成和 stemona 型脱氢对叶百部碱的不对称全合成研究。脱氢细花百部碱 didehydroparvistemonine 具有百部生物碱独有的吡咯[1,2-α]氮杂卓环和独特的手性五元内酯环并四氢呋喃环的双环结构。利用过渡金属 Ir/胺双元催化作为关键反应，通过一步反应高效的构建两个连续的叔碳手性中心，后采用 Krische 金属 Ir 催化、双键异构化高效选择性合成了手性五元内酯环，紧接着经 Grieco 消除、Wacker 氧化，CBS 不对称还原得到手性二级醇，最后经 DBU 促进分子内氧杂迈克加成环化得到了关键的双环结构并顺利完成了 didehydroparvistemonine 前体四环骨架的合成研究。; The thesis focuses on the asymmetric syntheses of quinocarcinamide precursor and didehydroparvistemonine precursor, which was carried out around the Ir-catalyzed asymmetric allylation reaction. It mainly includes the following two chapters. The first chapter describes the chemical synthesis of the tetrahydroisoquinoline alkaloid quinocarcin. Our research focused on the first critical stereogenic center, which was constructed by the Ir-catalyzed asymmetric allylamination reaction. The resulting product was oxidized to cleave the double bond and then reduced to obtain the corresponding primary alcohol, whose structure, including absolute configuration, was confirmed by a X-ray single crystallographic analysis. Next, the substituted allyl bromide was converted into a 1,3-cis-disubstituted tetrahydroisoquinoline ring system of (+)-quinocarcinamide through a three-step protocol including a Stille coupling reaction, a cross olefin metathesis reaction and a highly stereoselective SN2' reaction promoted by potassium tert-butoxide. The second chapter describes our research on the partial synthesis of parvistemoline and asymmetric total synthesis of bisdehydrotuberostemonine. Didehydroparvistemonine has the typical nucleus of pyrrole [1,2-α] azapetrope ring and an unusual bicyclic subunit fused through a substituted butyrolactone and tetrahydrofuran. Using Ir/amine dual catalysis as the key reaction, two consecutive tertiary carbon chiral centers were efficiently constructed through a one-step reaction. Then other key strategies included Ir-catalyzed Krische allylation, double bond isomerization of lactone ring five memberea, Grieco elimination, Wacker oxidization, and CBS asymmetrical reduction, affording chiral secondary alcohol. Finally, the DBU promoted intramolecular oxa-michael addition cyclization to get a critical bicyclic structure and completed the synthesis of the tetracyclic skeleton of the precursor of didehydroparvistemonine.
语种	中文
	2022-11
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75223
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	石莉. 生物碱 quinocarcinamide 和 didehydroparvistemonine 关键前体的合成[D]. 中国科学院大学,2022.

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