癌症干细胞在多种癌症发生、发展、复发、转移和耐药过程中发挥重要作用，因此，靶向癌症干细胞的药物研发至关重要。目前发现的可以清除癌症干细胞的化合物种类很少。缺少选择性杀灭癌症干细胞的先导化合物，限制了靶向癌症干细胞的新药研发。天然脂肽化合物JBIR-141是结构新颖，可以清除癌症干细胞的化合物。该化合物不但可以通过抑制Foxo3a的转录活性，抑制白血病干细胞，同时对多种普通肿瘤细胞有较强的抑制活性。目前还没有该化合物的全合成及其构效关系研究的报道。本项目拟对该化合物进行全合成，为该类化合物的合成和结构改造提出切实可行的工艺路线。随后制备类似物库，通过活性测试，探索其杀灭癌症干细胞的药效团与构效关系。据此设计与合成分子探针，研究该类化合物的作用靶点。本项目有望完成JBIR-141的首次全合成，建立杀灭癌症干细胞的构效关系，获得杀灭癌症干细胞的候选药物，为靶向癌症干细胞药物的设计与合成提供基础。

Cancer stem cells (CSCs) are responsible for cancer formation, progress, relapse, metastasis and resistance. Therefore, the development of medicine molecules targeting cancer stem cells plays vital role in medicinal researching area. However, the molecules that may selectively ablate CSCs are very rare. Due to lack of anti-CSCs leading compounds limits the R&D of drugs targeting cancer stem cells. The natural depsipeptides JBIR-141 was found as an anti-CSCs product with novel structure. This molecule was not only exhibited eradicating CML stem cells by inhibition against Foxo3a transcriptional activity, but also found strong anti-proliferation activity against several normal cancer cell lines. There is no report on total synthesis or SAR study of JBIR-141. This project aims to accomplish the total synthesis of JBIR-141. The analogues library will be prepared. Preliminary structure-activity relationship (SAR) against cancer stem cells will be concluded via bioassay. The molecular probe will be designed and synthesized based on the SAR to investigate the complex active site of targeting cancer stem cell. This project may not only accomplish the first total synthesis of JBIR-141 and obtain SAR against cancer stem cells, but also identify drug candidate targeting cancer stem cells, and elucidate more information for the design and synthesis of drugs inhibiting cancer stem cells.