Tian Tian, Zhu Zhiming, Ding Yalong, Li Guoli, Li Nan, Shen Tong
School of Chemical and Biological Engineering, Lanzhou Jiaotong University, Lanzhou, Gansu 730070, P. R. China.
ACS Omega. 2020 Dec 14;5(51):33478-33483. doi: 10.1021/acsomega.0c05546. eCollection 2020 Dec 29.
The first total synthesis of sanjoseolide (), which was originally obtained from A, was achieved via an efficient route with a longest linear sequence of six steps from the commercially available 2,4-dihydroxyacetophenone in 8.6% overall yield. Meanwhile, a series of sanjoseolide representative analogues were synthesized and assessed for their antiproliferative potency against cancer cells of different origins. Compound inhibited the survival of all tested cancer cell lines in a dose-dependent manner, the IC values of the treatment were about 12.8 μM for human cholangiocarcinoma cell lines RBE and 12.7 μM for human cholangiocarcinoma cell lines HCCC-9810, which was more active than sanjoseolide (). Analysis of the structure-activity relationships revealed that the presence of a trifluoromethyl group may be beneficial in terms of both RBE and HCCC-9810 inhibition.
最初从A中获得的圣何塞内酯（）的首次全合成是通过一条高效路线实现的，该路线以市售的2,4 - 二羟基苯乙酮为起始原料，最长线性步骤为六步，总收率为8.6%。同时，合成了一系列圣何塞内酯代表性类似物，并评估了它们对不同来源癌细胞的抗增殖能力。化合物以剂量依赖性方式抑制所有测试癌细胞系的存活，对于人胆管癌细胞系RBE，处理的IC值约为12.8 μM，对于人胆管癌细胞系HCCC - 9810，IC值约为12.7 μM，其活性比圣何塞内酯（）更高。构效关系分析表明，三氟甲基的存在对于抑制RBE和HCCC - 9810可能是有益的。
