丹参酮ⅡA和原人参三醇衍生物的制备及生物活性评价

	丹参酮ⅡA和原人参三醇衍生物的制备及生物活性评价; Synthesis of tanshinone ⅡA and propanaxtriol derivatives and evaluation of their biological activity
	陈爽
导师	赵勤实
摘要	Tanshinone IIA and protopanaxatriol are two small terpenoid molecules with natural biological activity in nature. They are mainly derived from the plants Salvia miltiorrhiza, Panax ginseng and Panax notoginseng. Using the successfully established screening model for the activity of key enzymes IDO1 and TDO in tumor immune escape, it was found that the precursor compound Tanshinone ⅡA has a moderate inhibitory activity on IDO1. In this study, the structural modification of Tanshinone ⅡA was continued by chemical means, and 25 different derivatives were obtained, of which 18 compounds have improved inhibitory activity against IDO1/TDO, and 6 compounds have excellent dual inhibitory activity against IDO1 and TDO, with IC50 values between 0.1 and 1 μM, at the same time, the relationship between the structure of tanshinone IIA and its inhibitory activity are evaluated. It was found that the benzo-o-quinone structure is an essential structure for activity, changes in the structure of the A ring and the D ring have a greater impact on the activity, in particular, when the three positions of the A ring and the methyl group of D ring are replaced by a hydrogen bond donor or acceptor atom, the inhibitory activity of IDO1/TDO has been significantly improved. At the same time, a stable and efficient method of obtaining active compounds has been explored. Inhibition of 11β-HSD1 has an important effect on the improvement of diabetes. The research group isolated a natural selective inhibitor of 11β-HSD1 Hupehenol B from Hubei Viburnum. Due to its low natural content, In the preliminary research work, our group completed the semi-synthesis of Hupehenol B from protopanaxadiol and explored the structure-activity relationship of derivatives. In this thesis, we starting from the natural product protopanaxatriol, which is rich in source and similar in structure, the key active intermediate 15 can be obtained through a three-step route, and made a preliminary exploration of the skeleton structure of protopanaxatriol, prepared 24 derivatives of protopanaxatriol with different structures. This job, laid an important foundation to the further study which the structure-activity relationship with 11β-HSD1 for tetracyclic triterpenoid derivatives and the evaluation of the biological activity of 11β-HSD1 in the later stage. Keywords: Tanshinone IIA; Protopanaxatriol; Preparation of derivatives; Biological activity evaluation.
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74514
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	陈爽. 丹参酮ⅡA和原人参三醇衍生物的制备及生物活性评价, Synthesis of tanshinone ⅡA and propanaxtriol derivatives and evaluation of their biological activity[D],2021.

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