A New Ultrasonic-Assisted One-Step Synthesis of Skin Lightening Bioactive Molecules by Using Fe/SiO2 as a Catalyst

α-Arbutin and its derivatives are widely recognized for their potent antioxidant activity and clinically validated skin-lightening effects. However, conventional synthetic strategies often rely on multistep protection-deprotection procedures, which reduce overall efficiency and limit scalability. The objective of this study was to develop a simple, one-step, and stereo- selective method for synthesizing α-Arbutin and related sugar derivatives using a heterogeneous solid acid catalyst under mild and sustainable reaction conditions.

An ultrasonic-assisted glycosylation protocol was developed using Fe/SiO₂ as a reusable solid acid catalyst. Reactions were performed with unprotected sugars in various solvents at 35-40 °C. Ultrasonic irradiation was employed to enhance reaction kinetics and mass-transfer efficiency. Reaction progress, stereoselectivity, and product purity were monitored using TLC, NMR, and HPLC analyses. Catalyst recyclability and structural stability were evaluated across several reaction cycles.

The protocol successfully produced α-Arbutin and multiple sugar derivatives in good to excellent yields (3a-3f). Ultrasonication significantly shortened reaction time while maintaining high product purity and selectivity. The Fe/SiO₂ catalyst exhibited strong acidity, high catalytic performance, and excellent reusability. Unprotected sugars afforded the desired α-anomer with remarkable stereoselectivity across different solvents. The method avoided protection- deprotection steps and generated minimal by-products, demonstrating operational simplicity and efficiency.

These findings highlight that coupling ultrasonic energy with a heterogeneous solid acid catalyst provides a greener, faster, and more selective glycosylation strategy that aligns with sustainable synthesis principles.

The ultrasonic-assisted Fe/SiO₂-catalyzed one-step synthesis offers an efficient, environmentally compatible, and stereoselective route for producing α-Arbutin and its derivatives (3a- 3f), supporting their potential application in cosmetic and pharmaceutical formulations.