A Photoenzymatic Pathway for Gram‐Scale Synthesis of 25‐Hydroxyvitamin D₃

Abstract

Vitamin D and its analogues play a crucial role in promoting the well‐being of both humans and animals. However, the current synthesis of this vital class of nutrients heavily relies on chemical transformations, which suffer from low step‐ and atom‐efficiency due to lengthy synthetic pathways. To enhance sustainability in the chemical industry, it is necessary to develop alternative synthetic processes. Herein, we present a photoenzymatic approach for synthesizing 25‐hydroxyvitamin D3 from 7‐dehydrocholesterol. In this sequential synthesis, 7‐dehydrocholesterol is initially hydroxylated at the C25 C‐H bond, resulting in an 85% conversion to 25‐hydroxyl‐7‐dehydrocholesterol. Subsequently, by employing photo‐irradiation using a monochromatic LED ultraviolet light source in a batch reactor and thermal isomerization, 25‐hydroxyvitamin D3 is obtained in satisfactory yield. This photoenzymatic process significantly reduces the need for purification steps and allows for gram‐scale synthesis of the target product. Our work offers a selective, efficient, and environmentally friendly method for synthesizing 25‐OH‐vitamin D3, addressing the limitations of current synthetic approaches.