【摘要】：目的：分離青黛中有效成分靛紅(ISA, isatin),對其進行結構改造得到一系列全新化合物,進行活性研究,為研發(fā)具有自主知識產(chǎn)權的靛紅類新藥打下基礎。 方法：1.用經(jīng)典的水蒸氣蒸餾法和層析分離方法從中藥青黛中分離ISA；2.運用國際前沿的有機合成方法,以ISA為骨架出發(fā)合成一系列全新的具有多個手性中心的3位吲哚氧雜螺環(huán)化合物并用1HNMR、13CNMR、HRMS進行結構鑒定：3.采用瓊脂平板二倍稀釋法測定底物、目標化合物及其衍生物對供試菌的最小抑菌濃度。 結果：1.青黛中ISA分離結果：得到純度高于90%的橙紅色晶體,與ISA標準品進行薄層層析對比得到相同的Rf值；2.結構改造結果：實驗過程中共合成22個化合物,包括16個均未見報道的目的化合物,所有目的化合物的結構都經(jīng)1HNMR、13CNMR、HRMS分析確證,并進行了熔點和旋光度的測定；3.對靛紅N位進行芐基修飾得到的產(chǎn)物可略微增加靛紅對某些菌種的抑制作用,而進一步改造得到的部分目標產(chǎn)物及其衍生物據(jù)初步研究沒有明顯的抗菌活性,體外抗腫瘤活性的初篩顯示其中有目標產(chǎn)物對前列腺癌細胞LNCaP的增殖有一定的抑制作用。 結論：以從青黛中分離的有效成分ISA為核心骨架的改造產(chǎn)物吲哚醌3位氧雜螺環(huán)化合物失去了原本的抗菌活性,推測靛紅的3-位羰基可能為ISA抗菌活性的有效基團。
[Abstract]:Aim: to obtain a series of new compounds by structural modification of indirubin (ISA, isatin), which is an effective component of Qingdai, and to study its activity so as to lay a foundation for the research and development of new indigo drugs with independent intellectual property rights. Methods: 1. Separation of ISA;2. from Qingdai traditional Chinese medicine by classical steam distillation and chromatography A series of novel 3-position indole-oxo heterocyclic compounds with multiple chiral centers were synthesized by using the advanced organic synthesis method in the world, using ISA as the framework and 1HNMR, 13CNMR. the structure of the compounds was identified as follows: 3. The minimal inhibitory concentration (MIC) of substrate, target compounds and their derivatives against tested bacteria was determined by Agar plate dilution method. Results: 1. The results of ISA separation in Qingdai showed that orange-red crystal with purity higher than 90% was obtained and the same RF value was obtained by thin-layer chromatography (TLC) with ISA standard; Results of structural modification: 22 compounds were synthesized during the experiment, including 16 unreported target compounds. The structures of all compounds were confirmed by 1HNMR, 13CNMR and HRMS, and the melting point and optical rotation were determined. The product modified by benzyl group on N site of Indigo can slightly increase the inhibitory effect of indirubin on some strains, but some of the target products and their derivatives obtained by further modification have no obvious antibacterial activity according to the preliminary study. The primary screening of anti-tumor activity in vitro showed that the target product could inhibit the proliferation of prostate cancer cell line LNCaP to a certain extent. Conclusion: the modified product of indolequinone-3-oxo-helicyclic compound with the core skeleton of ISA isolated from Qingdai has lost its original antibacterial activity. It is suggested that the 3-carbonyl group of indirubin may be the effective group of the antibacterial activity of ISA.
【學位授予單位】：成都中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R285

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