Studies toward the Total Synthesis of Xanthochymol

Xanthochymol, a polycyclic polyprenylated acylphloroglucinol (PPAP) natural compound, has demonstrated good anticancer and antimicrobial properties. However, no related studies on the synthesis of xanthochymol have been reported hitherto. In this study, 3,3-dimethylglutaric acid was used as the starting material to synthesize a key linear precursor via several steps, followed by a domino Dieckmann condensation reaction to construct the bicyclo[3.3.1]nonane-2,4,9-trione core skeleton. With that, the total synthesis of (+/-)-xanthochymol in 11 steps with a total yield of 10% has been first accomplished. By obtaining the side chain diastereomers of xanthochymol through this study, we have clarified the difference between them on the H-1 NMR and C-13 NMR spectra while at the same time provided references for future isolation, identification, and discrimination of xanthochymol from its side chain structural isomers.