Fawcettimine型石松生物碱中间体合成研究

	Fawcettimine型石松生物碱中间体合成研究; Synthesis of Fawcettimine type Lycopodium alkaloid intermediates
	欧玉飞
导师	赵勤实
摘要	Lycopodium alkaloids are mainly exist in Huperziaceae and Lycopodiaceae plants. In 1986, Chinese scientist Jiasen Liu separated Huperzine A from the traditional Chinese medicine Melaleuca, which was a highly effective acetyl choline esterase inhibitor (acetyl choline esterase, AChE). Huperzine A has become one of the research hotspots in the pharmaceutical field. This thesis focuses on the synthesis of Fawcettimine type Lycopodium alkaloid intermediates. The intermediate 6/6/5 tricyclic skeleton is the same as the B/C/D ring skeleton of Fawcettimine type Lycopodium alkaloids. The divergent synthesis of Fawcettimine-type alkaloids lays a foundation for new Fawcettimine type frameworks or new compounds, solving the problem of insufficient separation of target compounds and insufficient activity screening, and promotes further research. The 6/6/5 tricyclic tricarbonyl was obtained by oxidation/condensation of tricyclic enamine. The first method and the second method both use α,β-unsaturated ketones as starting materials, and (carbene reaction) cyclopropanation/ opening ring reaction as the key reaction. The first method was to construct the 6/5 bicyclic ring through the (carbene reaction) cyclopropanation/opening ring reaction, then the 6/5 bicyclic ring and the methylamine hydrochloride salt condensation reaction to construct the C ring. The second method was to add 4 M HCl to remove TBS on the basis of the first method in enol silyl ether, α,β-unsaturated ketone and methylamine hydrochloride condensation reaction to build the C ring, azoenamine through (carbene Reaction) cyclopropanation/opening ring reaction was constructed the B ring. The common features of the first method and the second method were synthesized of tricyclic enamine. The tricyclic enamine was obtained 6/6/5 tricyclic tricarbonyl through a two-step reaction compound. The two methods were used to synthesize 6/6/5 tricyclic framework compound by 9 steps. The total yield of the first method was 7%, and the total yield of the second method was 10%. The first method (carbene reaction) cyclopropanation/opening ring reaction was yielded of only 30%, and the second method (carbene reaction) cyclopropanation/opening ring reaction was yielded of 65%. The second method was more superior than the first method. Main features: the former four steps to synthesize α,β-unsaturated ketones can be amplified by 100 grams, and the Michael addition reaction, (carbene reaction) cyclopropanation/opening ring reaction and DMDO oxidation/TsOH condensation reaction can be amplified by 30 grams. The total synthesis of the new framework of Fawcettimine-type alkaloids was accomplished through 6/6/5 tricyclic dicarbonyl intermediates.
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74494
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	欧玉飞. Fawcettimine型石松生物碱中间体合成研究, Synthesis of Fawcettimine type Lycopodium alkaloid intermediates[D],2021.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
欧玉飞-欧玉飞-药物化学c8d026ae（6294KB）	学位论文		限制开放	CC BY-NC-SA	请求全文