Capsaicinol: Synthesis by Allylic Oxidation and Its Effect on TRPV1-Expressing Cells and Adrenaline Secretion in Rats

Abstract

Capsaicinol is an ingredient of hot red pepper. In this study, we developed a novel method for capsaicinol synthesis and examined capsaicinol’s physiological effects on capsaicin receptor (TRPV1)-related actions. Allylic oxidation of capsaicin by palladium acetate (Pd(OAc)₂) resulted in the formation of (±)-capsaicinol acetate at a 7.2% yield in a single step. The effectiveness of (±)-capsaicinol in TRPV1 activation (EC₅₀=1.1 μM) was found to be weaker than that of capsaicin (EC₅₀=0.017 μM), whereas the efficacy of (±)-capsaicinol reached 75% of that of capsaicin. Intravenous administration of (±)-capsaicinol in anesthetized rats dose-dependently enhanced adrenaline secretion from the adrenal gland. The response to a 5 mg/kg-dose of (±)-capsaicinol was comparable to that of a 0.05 mg/kg-dose of capsaicin. The relative pungency of capsaicinol to capsaicin was coincident with the relative effectiveness in inducing these TRPV1-related actions.