The Total Synthesis of (±)-Royleanone

The total synthesis of (±)-royleanone (I) has been achieved. 5,7,8-Trimethoxy-1-tetralone (III) was converted into (±)-5,7,8-trimethoxy-1-methyl-2-tetralone (VII) via a dihydronaphthalene derivative (IV). The annelation of VII with methyl vinyl ketone gave a (±)-hexahydro-2-oxophenanthrene derivative (VIII), which was then further converted into (±)-11,12,14-trimethoxy-3-oxopodocarpa-5,8,11,13-tetraene (IX). The hydro-genation of IX over platinum oxide gave two dihydro derivatives, (X) and (XI), in a ratio of ca. 1 : 7, these configurations in the A/B ring juncture were identified as trans and cis respectively. Therefore, IX was subjected to thioketalization, followed by desulfurization, to give (±)-11,12,14-trimethoxypodocarpa-5,8,11,13-tetraene (XV). The hydrogenation of XV over 10% palladium on carbon gave (±)-11,12,14-trimethoxypodocarpa-8,11,13-triene (XII), along with a small amount of its cis isomer (XIII). Finally, XII was converted into a hydroxy-1,4-quinone derivative (XIX), which was then treated with isobutyryl peroxide to give (±)-I, whose IR, UV, and NMR spectra were identical in every respect with those of natural royleanone.