Insulicolide A的全合成和结构优化

Insulicolide A是从加勒比海绿藻的共附生真菌曲霉 Aspergillus insulicola (MD10-2)中分离得到的一种倍半萜类化合物，具有显著的肿瘤细胞抑制活性。通过一组对60个人类肿瘤群的抑制活性测试，显示该化合物对60个人类肿瘤群的IC50平均值为1.1 mg／L，此结果充分揭示了该化合物对各类肿瘤细胞的抑制范围之广泛，因而可能具有极好的应用前景。Insulicolide A具有独特而复杂的[6-6-5]多环内酯骨架，其中含有五个连续的手性中心，包含三个季碳中心，并且在其C6位上还含有天然产物中较为罕见的对硝基苯甲酸酯片段。 Insulicolide A引起本课题组极大的研究兴趣是由于：1.该天然产物对多种肿瘤细胞均具有显著的抑制活性；2.化合物具有复杂多环内酯骨架结构，五个连续的手性中心（包含三个季碳），以及含有天然产物中较为罕见的对硝基苯甲酸酯片段等结构特点

Insulicolide A is a sesquiterpenoid obtained from Aspergillus insulicola (MD10-2) accreting with the Caribbean Sea algae. It possesses significant anti-tumor activity. The compound shows a mean IC50 of 1.1 mg/L towards 60 human cancer cell-lines and this result confirms its broad anti-tumor activity and makes it a good application future. Beside, Insulicolide A has a complicated [6-6-5] poly-cyclic lactone skeleton which possesses 5 continuous chiral centers, including 3 quaternary carbon centers, and a rare para-nitrobenzoic ester on C6 position. The reason of Insulicolide A attracting our research interests are: 1. this natural product shows remarkable anti-tumor activity towards kinds of cancer cell-lines. 2. its structure features including a complicated [6-6-5] poly-cyclic lactone skeleton possessing 5 continuous chiral centers (3 quaternary carbon centers) and a rare para-nitrobenzoic ester.