Gukulenin类天然产物的合成研究

Gukulenin类天然产物是从海洋海绵Phorbas gukulensis的次级代谢产物中分离得到一类杂二聚型天然产物，其全合成具有很大的挑战性。生物活性研究数据表明Gukulenin类天然产物具有非常好的抗癌活性：其中，Gukulenin A对人类咽喉癌细胞具有极强的抑制活性(IC50=57 nM)，对肾癌细胞也表现出非凡的抑制活性(IC50=92 nM)。因此，开展Gukulenin类天然产物及相应的类似物的合成研究，具有重要的科学意义和潜在应用价值。此项目针对这类复杂天然产物开展全合成研究，拟采取汇聚式合成策略，实现单体的偶联，为此类天然产物的构效关系等药物化学研究奠定基础。

Gukulenins are a family of hetero-dimeric natural products, which were isolated from secondary metabolites of marine sponge Phorbas gukulensis. Total synthesis of this group of natural molecules is a challenging project due to their complex structural features. Biological studies reveal that Gukulenins show potent activities against several of human cancer cells. Among them, Gukulenin A exhibited potent activities against human pharynx cancer FaDu (IC50=57 nM), and renal cancer SN12C (IC50=92 nM). Therefore, total synthesis of these natural products and their derivatives has great significance to both academic field and potential applications in pharmaceutical. This research program will carry out a convergent total synthesis of this family of natural products which will lay a solid foundation for the structure-activity relationship and related medical chemistry studies.