Abstract
In nature, polycyclic phloroglucinols are a class of compounds with considerable structural diversity and promising biological activities. Herein, we present an improved one-pot method that replaces the solution reaction conditions by mixing the reactants with column chromatography silica gel. Through this convenient, mild, slow, and diversity-oriented strategy, eight structurally unique polycyclic phloroglucinols were discovered, of which compound 1 possesses a rare cage-like skeleton. All compounds determined their structures by X-ray diffraction. Compared with traditional methods, this synthetic strategy produced better diversity and unique structures under milder conditions, suggesting that this method has great potential in lead compound discovery. The optimal reaction conditions were determined by high-performance liquid chromatography (HPLC) monitoring over time. In addition, density functional theory (DFT) calculations were performed to investigate the possible generative pathway of compound 1. We also examined the neuroprotective actions of selected compounds on SH-SY5Y cells and the MPP+-induced Caenorhabditis elegans PD model.