Synthesis and Cytotoxic Evaluation of Sanjoseolide and Representative Analogues.

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.