The Synthesis of (+)-Premnolal

Abstract The revised structure of premnolal was confirmed by the following synthesis. Treatment of 12-methoxypodocarpa-8,11,13-triene (7), derived from methyl 12-methoxypodocarpa-8,11,13-trien-18-oate, with ethoxyoxalyl chloride and anhydrous aluminium chloride afforded 13-(ethoxyoxalyl) derivative, which was converted into 12-hydroxypodocarpa-8,11,13-triene-13-carbaldehyde (9) by alkaline hydrolysis, decarboxylation, and demethylation. The compound 9 was also prepared from 7 by demethylation and formylation. Reduction of 9 with lithium aluminium hydride, followed by partial acetylation, afforded 13-acetoxymethyl derivative which was converted into 13-acetoxymethyl-12-methoxy-11-nitropodocarpa-8,11,13-triene by nitration and methylation. This was then converted into 11,12-dimethoxypodocarpa-8,11,13-triene-13-carbaldehyde (18) by a series of reactions: catalytic hydrogenation, diazotization, reduction with lithium aluminium hydride, methylation, and oxidation. Demethylation of 18 gave 11,12-dihydroxypodocarpa-8,11,13-triene-13-carbaldehyde, which was identical with natural premnolal.