Concise synthesis of deuterium-labelled proanthocyanidin metabolite 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone as an analytical tool

Abstract

Deuterated proanthocyanidin metabolite 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone has been successfully produced. This metabolite is responsible for several proanthocyanidin protective effects in the field of cancer chemoprevention, skin wrinkle-prevention, and antimicrobials. The synthetic approach applied employs a short reaction sequence and allows the incorporation of four deuterium atoms on non-exchangeable sites, making it an attractive strategy to produce a stable isotopically labeled internal standard for quantitative mass spectrometry isotope dilution-based methods, as demonstrated by developing an LC-MS/MS method to quantify DHPV in urine samples. Overall, this efficient synthesis provides a valuable analytical tool for the study of the metabolic conversion of proanthocyanidins thus helping to investigate the biological effect and establishing the active dose of the key catabolite 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone.