Chemical synthesis and tyrosinase inhibitory activity of resorcinol alkyl glucosides, hydroxyalkyl resorcinols, and alkyl resorcinols

• Published in: Journal of molecular structure Vol. 1268; p. 133668
• Main Authors: Ishioka, Wakana, Nihei, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-11-2022
• Subjects: Alkyl resorcinol; Hydrophilic tyrosinase inhibitor; Hydroxyalkyl resorcinol; Koenigs-knorr glycosylation; Resorcinol alkyl glucoside; Wittig reaction; Alkyl resorcinol; Wittig reaction; Hydroxyalkyl resorcinol; Resorcinol alkyl glucoside; Koenigs-knorr glycosylation; Hydrophilic tyrosinase inhibitor
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133668

•Resorcinol alkyl glucosides 7–12 were synthesized to develop tyrosinase inhibitors.•Hydroxyalkyl resorcinols 13–18 and alkyl resorcinols 19–24 were also evaluated.•The approach of the sugar and hydroxy groups to the resorcinol reduces the activity.•The activity of alkyl resorcinol 24 is decreased due to the poor water solubility.•The distance between the resorcinol and hydrophilic group is essential for activity.
To develop novel tyrosinase inhibitors, resorcinol alkyl glucosides 7–12 were synthesized via the Wittig and/or Horner-Wadsworth-Emmons reactions with Koenigs-Knorr glycosylation as the key step. Half maximal inhibitory concentrations (IC50) of 35.9–0.39 µM were observed for 7–12 for the tyrosinase-catalyzed oxidation. Tyrosinase inhibitory activity of hydroxyalkyl resorcinols 13–18 and alkyl resorcinols 19–24 were also evaluated to investigate the effect of sugar in their structures. As a result, the IC50s of 13–18 and 19–24 were 9.27–0.32 µM and 1.58–0.53 µM, respectively. Most of the derivatives became more potent with the increasing length of the alkyl chain. The gap in the activities between the C2 and C3 analogs was decreased in the order: resorcinol alkyl glucosides>hydroxyalkyl resorcinols>alkyl resorcinols. It indicates that the sugar and hydroxy groups interfered in the functions when they were adjacent to the resorcinol ring. C14 analog 22 (IC50 = 0.81 µM) with the poor water solubility showed slightly weak activity compared with the C10 analog 21 (IC50 = 0.53 µM). Thus, the modification of a prescribed distance, at least, the C3 alkyl spacer, between the resorcinol ring and sugar or hydroxy group is a requisite to effectively design a potent, hydrophilic tyrosinase inhibitor.
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