Chemical synthesis and tyrosinase inhibitory activity of rhododendrol glycosides

• Published in: Bioorganic & medicinal chemistry letters 2014-01, Vol.24 (1), p.122-125
• Main Authors: Iwadate, Takehiro, Kashiwakura, Yutaka, Masuoka, Noriyoshi, Yamada, Yoichi, Nihei, Ken-Ichi
• Format: Article
• Language: English
• Subjects: Benzaldehyde; Butanols - chemical synthesis; Butanols - chemistry; Butanols - pharmacology; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - pharmacology; Molecular Structure; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.11.063

The concise synthesis of rhododendrol glycosides 3-8, which are novel derivatives of (+)-epirhododendrin (1) and (-)-rhododendrin (2), has been achieved in six steps from benzaldehyde 9. The key reactions include aldol condensation and trichloroacetimidate glycosylation. From biological studies, it has been determined that synthetic derivatives of 1 and 2 possess potent tyrosinase inhibitory activity. Particularly, the inhibitory activity of cellobioside 8 (IC50=1.51μM) is six times higher than that of kojic acid. The R-epimers (4, 6, and 8) possessed more potent activity than the corresponding S-epimers (3, 5, and 7), indicating that tyrosinase inhibitory activity is significantly governed by stereochemistry of rhododendrol glycosides.