一些海洋吲哚生物碱的合成与其生物靶点确认研究

Based on the fundamental organic reaction mechanisms, there is an urgent need to develop cost efficient synthetic routes towards complex biologically-active natural product synthesis. It is also a great challenge in organic chemistry. Our research is focusing on the syntheses of versicamide H，neosartoryadins A , B，norquinadoline A，deoxynortryptoquivaline and tryptoquivaline which were isoltaed from marine fungal and have proven to have good biological activities. These would need to develop a simple and efficient approach to access the nature products. Our design would facilitate a relative large-scale synthesis which would bring enough materials for the further structure-activity relationship studies. DARTS (Drug Affinity Responsive Target Stability) is a new technique based on the principle that when a small molecule compound binds to a protein. This technique is universally applicable for drug screening and target identification. In addition, we are going to prepare a library of natural or “non-natural natural products” for drug discovery studies via the function-oriented synthesis (FOS)。

基于对有机反应机理的深入了解，使用路线短、成本低的合成策略来合成具有重要生理活性的复杂天然产物是当前国际有机合成界急于解决的课题。同时随着药物研发要求的不断提高，活性分子的药物靶标研究也面临巨大的挑战。我们以近期从海洋中分离的，结构新颖的versicamide，neosartoryadins A和B，及其类似物norquinadoline A，deoxynortryptoquivaline与tryptoquivaline等吲哚生物碱作为研究对象，发展有效的合成策略进行高效的全合成，解决天然产物分离的资源瓶颈。接着通过一种基于蛋白组学、用于小分子药物筛选及靶标寻找的新技术（darts）对合成产物进行靶点确认，此外，使用功能导向合成(FOS)方法，对天然产物进行结构改造，设计出具有更优良活性表现的“非天然的天然产物”用于进一步的药学研究，以期研发出药效更佳更适于临床应用的新药。