Concise synthesis of 7-dehydrocholesterol and 25-hydroxy-7-dehydrocholesterol

Yan-Xin Yue; De-Jie Zhang; Jia-Jie Xu; Hao-Jie Ni; Xiang-Zhong Gu; Chen-Chen Li; Wen-Wei Qiu

doi:10.1016/j.steroids.2026.109801

Concise synthesis of 7-dehydrocholesterol and 25-hydroxy-7-dehydrocholesterol

Steroids. 2026 May 15:233-234:109801. doi: 10.1016/j.steroids.2026.109801. Online ahead of print.

Authors

Yan-Xin Yue¹, De-Jie Zhang¹, Jia-Jie Xu¹, Hao-Jie Ni², Xiang-Zhong Gu³, Chen-Chen Li⁴, Wen-Wei Qiu⁵

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Chemical Engineering, East China Normal University, Shanghai 200062, China.
² Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Chemical Engineering, East China Normal University, Shanghai 200062, China; ECNU-JIAERKE Pharm. Steroids Green Manufacturing Laboratory, East China Normal University, Shanghai 200241, China.
³ Department of Research and Development, Jiangsu Jiaerke Pharmaceuticals Group Co., Ltd., Zhenglu Town, Changzhou 213111, China; ECNU-JIAERKE Pharm. Steroids Green Manufacturing Laboratory, East China Normal University, Shanghai 200241, China.
⁴ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Chemical Engineering, East China Normal University, Shanghai 200062, China; ECNU-JIAERKE Pharm. Steroids Green Manufacturing Laboratory, East China Normal University, Shanghai 200241, China. Electronic address: li_ccqibebt@163.com.
⁵ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Chemical Engineering, East China Normal University, Shanghai 200062, China; ECNU-JIAERKE Pharm. Steroids Green Manufacturing Laboratory, East China Normal University, Shanghai 200241, China. Electronic address: wwqiu@chem.ecnu.edu.cn.

PMID: 42142606
DOI: 10.1016/j.steroids.2026.109801

Abstract

7-Dehydrocholesterol (7-DHC) and its hydroxylated product, 25-hydroxy-7-dehydrocholesterol (25-OH-7-DHC), exhibit diverse biological activities and serve as key precursors in the industrial synthesis of vitamin D₃ (VD₃) and 25-hydroxyvitamin D₃ (25-OH-VD₃). Consequently, various synthetic routes for 7-DHC and 25-OH-7-DHC have been proposed. Herein, we report a concise and practical synthetic route to 7-DHC (64% total yield) and 25-OH-7-DHC (44% total yield), using commercially available cholesterol and 25-hydroxycholesterol as the starting materials, respectively. The key reaction conditions, including solvent choice, temperature, base, and additive, were systematically investigated and optimized. This innovative synthetic route provides a cost-effective strategy for the potential large-scale production of 7-DHC and 25-OH-7-DHC.

Keywords: 25-Hydroxycholesterol; 25-Hydroxyl-7-dehydrocholesterol; 7-Dehydrocholesterol; Cholesterol.