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

1. Curr Org Synth. 2026 Jun 1. doi: 10.2174/0115701794451807260523105542. Online ahead of print. A New Ultrasonic-Assisted One-Step Synthesis of Skin Lightening Bioactive Molecules by Using Fe/SiO2 as a Catalyst. Mondal S(1), Dangate MS(1), Shaikh N(2). Author information: (1)Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology-Chennai Campus, Vandalur- Kelambakkam road, Chennai, Tamil Nadu, 600127, India. (2)College of Military Engineering, Maharashtra, Pune, 411031, India. INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. DOI: 10.2174/0115701794451807260523105542 PMID: 42253203