【作者】 马旭；

【导师】 赵伟杰； 李悦青；

【作者基本信息】 大连理工大学 ， 药物工程， 2010， 硕士

【摘要】 莪术油是中药莪术的有效成分,具有抗肿瘤、抗病毒、抗炎等功用。莪术醇是莪术油的有效成分之一,是一种具有发展前途的抗肿瘤药物。迄今为止,采用有机化学方法对莪术醇进行结构修饰的报道较少。本文研究了莪术醇在酸性条件下的芳构化反应,借鉴丙酮与莪术醇的芳构化反应,选择氢溴酸作催化剂,四氢呋喃作溶剂,选取不同的羰基化合物与莪术醇进行反应,制取了一系列的具有卓酮结构的化合物,收率在40.3-75.0%；基于反应中得到的中间体,提出芳构化的机理,并对3个卓酮化合物进行了X-ray单晶衍射分析。通过对机理的研究发现：羰基化合物的羰基在酸性条件下被活化生成碳正离子的稳定性及空间位阻是影响反应的主要因素,羰基活性较低及空间位阻较大的羰基化合物不能与莪术醇发生芳构化反应。论文还通过氢化、重排、氧化、开环等反应对莪术醇进行结构修饰,制得氢化莪术醇(化合物11)、莪术醇开环产物(化合物13)、9,10环氧化物(化合物14),9位羟基化衍生物(化合物15)等,在结构修饰的过程中发现莪术醇在氢氧化钾催化下可以转化为双键迁移到环内的产物(化合物12),通过改进反应条件,收率可达到93.0%。对化合物12和15进行了X-ray单晶衍射分析,确定其立体构型。结合单晶数据分析,对环氧化反应、环氧环开环反应的机理和立体化学进行了深入探讨。更多还原

【Abstract】 Curcuma oil is the active ingredient of curcuma which is a traditional Chinese medicine. It has anti-tumor, anti-virus, anti-inflammatory and other functions. Curcumol is one of the active ingredients of curcuma oil. It is a promising anticancer drug. Up to now, there are few reports on structural modification of curcumol by organic methods.In this paper, we study the aromatization of curcumol under acidic conditions. Aromatization of curcumol with acetone is selected as the model reaction in this paper. Hydrobromide is selected as catalyst and tetrahydrofuran as solvent. Based on model reaction, a series of new trienone compounds have been prepared by curcumol reacting with different carbonyl compounds in the yield of 40.3-75.0%. And we proposed mechanism of aromatization. Three trienone compounds’X-ray diffraction data are analyzed. During the study of mechanism, we find that:the stability of carbonium generated from the carbonyl compounds and steric hindrance are the main factors affecting the aromatization. Carbonyl compounds with lower activity and larger steric can not have aromatization with curcumol.In our study, the structural modification of curcumol is also carried out by hydrogenation, rearrangement, oxidation and ring opening reaction. We got hydrogenated curcumol (compound 11), open loop product of curcumol(compound 13),9,10-epoxide(compound 14) and 9-hydroxy derivatives(compound 15), etc. And in the process of structural modification of curcumol, we find that the double bond of curcumol can migrate into the ring under catalysis of potassium hydroxide. After improving the reaction conditions, we get a higher yield of 93.0%. Three-dimensional configuration of compound 12 and 15 is determined based on X-ray diffraction data analysis. We have a thorough discussion of the epoxidation and ring opening reaction mechanism and stereochemistry.更多还原