Walsucochin A及其类似物的合成研究

Nature products and natural product-like molecules have been important sources for the discovery and development of new medicines. Nature products with [6/6/5/6] skeleton are often isolated in very low quantities from their natural sources. Due to the novel structural features, remarkable biological activities and scarcity of material, syntheses of these natural products have been of great interest in recent years. However, developing efficient approaches to these complex terpenoids is still challenging, which has hampered the detailed biological evaluations of these natural products. The aim of this project is to develop an efficient synthetic route to the nortriterpenoids walsucochin A and the related analogs. Walsucochins A was isolated from Walsura cochinchinensis and has [6/6/5/6] skeleton. This project is towards developing radical tandem cyclization reaction to form ABC rings, gold-catalyzed annulation reaction to form D ring, and further modification to give walsucochin A and the related analogs. The discovery of candidates for new drugs based on their bioactivities of synthetic intermediates and natural products are also investigated.

天然产物及类天然产物是发现和发展新药的重要源泉。[6/6/5/6] 四环系的稠环分子骨架广泛存在于许多活性天然产物中，具有广泛的生物活性。然而由于此类化合物在自然界中含量极低，且复杂的稠环分子结构使其高效合成具有很大的挑战性，该现状制约其进一步的生物活性评价。本项目以具有[6/6/5/6] 四环系的walsucochin A及其类似物为研究对象，探索利用自由基的串联反应一步构筑ABC环，利用金催化的环化反应构筑D环的合成策略及方法，经结构修饰最终实现相关天然产物的全合成；对合成的反应中间体及天然产物进行活性筛选，并进行一定的结构修饰和衍生化，建立天然产物类似物化合物库，筛选高活性化合物，为进一步新药研发奠定基础。

天然产物及类天然产物是发现和发展新药的重要源泉。[6/6/5/6]四环系的稠环分子骨架广泛存在于许多活性天然产物中，具有广泛的生物活性。然而由于此类化合物在自然界中含量极低，且复杂的稠环分子结构使其高效合成具有很大的挑战性，该现状制约其进一步的生物活性评价。本项目选取[6/6/5/6]四环系的walsucochin A及其类似物为研究对象，以法尼基溴为起始原料，利用钛试剂引发的自由基串联反应一步构筑ABC环，利用铜催化的配体导向C-H键活化反应选择性地引入7-羟基，利用迈克尔加成-Aldol缩合串联反应引入芳香D环等合成策略及方法，经结构修饰最终实现相关天然产物的全合成。通过对合成的反应中间体及天然产物进行的农用活性筛选，发现[6/6/5/6]四环系化合物具有较高抗真菌活性，这为进一步新农药的研发奠定基础。