Tetramic Acid类天然产物的仿生合成研究

Tetramic acid类天然产物是自然界广泛存在，且具有广泛生物活性的化合物。代表性分子包括Equisetin、Fusarisetin A、Diaporthichalasin及Integramycin。Equisetin属于真菌代谢物，具有细胞毒性，抗菌，HIV抑制性等。Fusarisetin A是从真菌代谢物中分离得到。作为有效的腺泡抑制剂，有可能成为新型的治疗癌症的药物先导化合物。针对此类天然产物有相关的化学合成报道，但是迄今为止还没有相关仿生合成报道。..本项目首次开展针对tetramic acid类天然产物的仿生合成研究，实现代表性分子Equisetin和Fusarisetin A的仿生合成，并以此为基础探索Diaporthichalasin 和Integramycin 的仿生合成途径，具有重要的学术意义。为评估和筛选此类天然产物的药用活性奠定了基础，具有潜在应用价值。

The naturally occurring tetramic acid type natural products have attracted a great deal of interest because the majority of the compounds isolated to date exhibit some biological function. Representative tetramic acids include Equisetin, Fusarisetin A, Diaporthichalasin and Integramycin. Equisetin, a fungal metabolite isolated from the white mold Fusarium equiseti, exhibits potent antibiotic and HIV inhibitory activity. Fusarisetin A was isolated from a soil fungus, Fusarium sp. FN080326. As a potent inhibitor of acinar morphogenesis, as well as cell migration and invasion without apparent cytotoxicity, it has the potential to become a new antitumor drug. Though chemical synthesis of this type natural products were achieved, there is no strategy base on the biosynthetic pathway reported...We plan to develop a novel strategy to prepare equisetin and fusarisetin A base on the biosynthetic pathway. The key step is Lewis acid promoted cascade reaction including the intramolecular Diels-Alder reaction and epoxide opening attacked by silyl-enol ether.Using similar strategy, we will also explore the biomimetic total synthesis of Diaporthichalasin and Integramycin.Derivatives and analogues of equisetin and fusarisetin A will be prepared base on the above strategy for further biological studies.