Synthesis of 8β-hydroxy-9(11),13-abietadien-12-one from (+)-dehydroabietylamine and its AhR ligand activity

Abstract

8β-Hydroxy-9(11),13-abietadien-12-one (1), an abietane diterpenoid and an aryl hydrocarbon receptor (AhR) ligand, was synthesized in six steps from commercially available (+)-dehydroabietylamine (2). We used the hypervalent iodine catalyst phenyliodine dicarboxylate, a safer alternative to toxic organoselenide reagents, for the oxidative dearomatization of ferruginol (7) to compound 1. Compounds 1 and 2, as well as the synthetic intermediates (compounds 3–7), were evaluated for AhR ligand activity. Only compounds 1 and 7 were active, which suggests that AhR affinity is influenced by the steric environment around the C-18 position of these compounds.

Keywords

• Abietane diterpenoid
• Aryl hydrocarbon receptor
• Safer reagent