Research Article | Open Access

Volume 2025 |Article ID 100025 | https://doi.org/10.1016/j.bidere.2025.100025

Efficient synthesis of clascoterone via lipase-catalyzed solvent-free alcoholysis

Qian Li,^1,2 Mingpeng Li,^1,2 Ling Wang,^1,2 Xiaojuan Yu,¹ Yuling Zhou,¹ Chenghua Gao ,¹ and Aitao Li ¹

¹State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, 430062, PR China
²These authors contributed equally to this work

Abstract

Clascoterone (cortexolone 17α-propionate), a novel therapeutic agent for acne, provides enhanced safety and efficacy over conventional therapies. However, the traditional synthesis of clascoterone, especially the final step, suffers from the use of hazardous and excessive organic solvents, along with suboptimal yields due to side reactions and incomplete conversion, which poses environmental and economic challenges. In this study, we developed a regioselective solvent-free alcoholysis method with the commercially available immobilized lipase Novozyme 435 as a catalyst and isopropanol (IPA) as an alcohol donor, achieving a conversion rate of over 98.0 % with 20 g/L substrate. Furthermore, we implemented a continuous flow microreactor process that increased the conversion rate to 100 % with 4 g/L substrate, demonstrating scalability for industrial manufacturing.