灵菌红素及其类似物的合成与性能研究

Podigiosin derivatives have special chemical and supromolecular properties, with excellent biological activities in anti-cancer and immunosuppression area. Their synthesis and production have attracted wide research interests. Currently, the design and development of this type of compounds are under-developed, and few compounds have been developed, making it difficult to study the structure-property relationship of this type of compounds. The avaliable organic synthetic methods for this type of compounds often suffer from the complex synthetic route, the limited substrate scope and the usage of expensive transition-metal (Pd) catalyst. It is very necessary to develop novel synthetic method for this type of compounds..Based on the reaction between pyrrole and azafulvene, in this project, we designed three novel synthetic routes for the efficient constrcution of prodigiosin derivatives, in which the usage of expensive transition-metal catalyst is avoided and the synthetic route is simplified. In addition, we also explored the possibility of using intramolecular (oxidative) Heck and Friedel-Crafts reactions or the construction of novel complicated prodigiosin derivatives. In this project, we will synthesize a series of novel prodigiosin derivatives, study their photophyscial properties, cell-localization, and biological activies, and analyze their structure-property relationship. We anticipate the development of several novel leading prodigiosin derivatives from this project, with excellent potential anti-cancer properties for the clinical treament of cancer. This project may provide good reference for the further development of other anti-cancer reagents.

灵菌红素(prodigiosin)衍生物具有一系列特殊的化学和超分子性质，在抗癌和免疫抑制等方面呈现优越的生物活性。目前该类化合物的种类仍然有限，缺乏进行构效关系研究的基础。现有有机合成方法大都存在路线复杂、底物适用范围窄和使用昂贵过渡金属钯催化剂等问题，迫切需要开发新型合成方法。.本项目以氮富烯和吡咯间的反应为基础，设计了三种制备灵菌红素及其类似物的新型合成方法，简化了合成路线。探索利用分子内（氧化）Heck和傅克反应来构建复杂灵菌红素衍生物的新型方法。本项目将构建一系列新型灵菌红素及其类似物，研究其光学性质和生物活性，分析构效关系，以期开发出性能良好的新型灵菌红素类抗癌先导化合物。该项目的成功开展将为进一步设计开发新型灵菌红素类抗癌试剂提供参考。

灵菌红素是存在于多种细菌、放线菌的次级代谢产物中的红色抗生色素。该类分子具有一系列特殊的化学和超分子性质，具有多种生物活性作用，例如抗癌，抗疟疾和免疫抑制等作用。目前合成该类骨架分子最有效的方法分别使用了Suzuki偶联作为关键步骤，存在使用过渡金属钯催化剂，底物适用范围较窄，尤其是含硼酸的吡咯；底物不稳定等问题。. 本项目利用共轭体系稳定氮富烯，发展了几种吡咯（氧化）直接取代氮富烯构建灵菌红素骨架的新型方法。利用吡咯的亲核性直接取代亲电性的（卤代）氮富烯衍生物，无需金属催化，高效合成了一系列新型灵菌红素衍生物。这种吡咯与氮富烯的新型反应有望用于其他多吡咯体系的合成。同时本项目合成的一系列多吡咯化合物可在荧光标记、离子识别和抗癌试剂等方面找到潜在应用。本项目的成果将为发展新型灵菌红素类化合物的合成和应用提供有效推动。