天然产物藤黄酸及其类似物的全合成和抗肿瘤构效关系研究

项目名称： 天然产物藤黄酸及其类似物的全合成和抗肿瘤构效关系研究

项目编号： No.30873157

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 王进欣

作者单位： 中国药科大学

项目金额： 34万元

中文摘要： 本课题采取循序渐进的原则进行选择性化学合成，以Claisen 重排/Diels-Alder 加成级联反应和Wittig－Horner 反应形成双键为关键步骤进行藤黄酸及其类似物的全合成研究，首次设计完成一条可行性较好的全合成路线。同时结合藤黄酸初步构效关系，进一步完成分子多样性的化学合成和抗肿瘤生物活性研究,在此基础上系统进行藤黄酸抗肿瘤构效关系的研究,设计合成出抗肿瘤活性显著、结构更优化、毒副作用小的新型抗肿瘤先导化合物.本课题将全合成研究与分子多样性的化学合成研究有机结合起来，相辅相承，提高了确立藤黄酸完整构效关系的可能性,同时促进藤黄酸及其类天然产物在合成、药理、药代动力学、分子生物学、抗肿瘤作用机制等方面的研究的发展 ，对于发现新的抗肿瘤临床药物具有深远意义。

中文关键词： 藤黄酸;全合成；抗肿瘤生物活性;构效关系

英文摘要： In research of this subject our work mainly involves in the selective chemical synthesis. In the procedure of discovering, we progress step by step in an orderly way.. The total synthesis of Gambogic acid and its analogues will be carried out by employing Claisen rearrangement/ Diels-Alder addition cascade connection and Witting-Horner reaction to form the double bond as key steps. At the same time, based on the fundamental SAR of Gambogic acid we will make further discoveries of the diversityoriented synthesis and anti-carcinoma activity of Gambogic acid. Following we have a deeper study of the SAR of the anti-tumour activity , which candiscover the more ideal lead compounds with higher activity, optimized structure and lower toxicity. We first combine the study of the total synthesis of Gambogic acid and its analogues and the study of diversity-oriented synthesis to form an organic entity sothat the possibility of establishing the complete SAR is enhanced considerably and the research of many respects of pharmaceutical science such as chemical synthesis,pharmacology, pharmacokinetics, molecular biology and anti-carcinoma mechanism isgreatly promoted. In one word, the achievements of our research will significantly contribute to the discoveries of new anti-tumour drugs.

英文关键词： gambogic acid; total synthesis;anti-tumour activity; relationships of structure and activity