Application of photoreactors in the experiment of photocatalytic synthesis of steroid natural products-Shanghai 3S Technology

Researchers from Jia-Jing Wu’s group at Shanghai Jiao Tong University have developed a photocatalytic strategy for the efficient synthesis of steroid natural products, harnessing the power of photoreactors to achieve precise stereochemical control. This innovative approach significantly streamlines the production of bioactive molecules such as (25S)-Δ7-Dafachronic acid, Demissidine, and Smilagenin—key compounds with potential applications in anti-parasitic agents, cancer therapies, and neuroprotection.

Key highlights of the study:

Precision editing of C-H bonds: The team employed photoreactors to selectively cleave tertiary C-H bonds in steroid scaffolds, enabling the construction of critical C5 and C25 stereochemical centers. This strategy overcomes traditional challenges in regional and stereoselectivity control.
Sodium decatungstate (NaDT) as the photocatalyst: Inspired by Wendlandt’s work, NaDT was used as a hydrogen atom abstraction (HAA) reagent to generate radical intermediates. By manipulating substrate design, the team achieved unprecedented C5/C25 epimerization with high diastereoselectivity (e.g., 96:4 dr for Δ7-Dafachronic acid).
Streamlined synthesis pathways: Using cheap starting materials (e.g., chenodeoxycholic acid), the team demonstrated concise routes to target molecules. For example, Δ7-Dafachronic acid was synthesized in 10 steps with 40% overall yield, representing the most efficient route to date.
Versatility across diverse scaffolds: The strategy was successfully applied to Demissidine (5-step synthesis, 48% yield) and Smilagenin, showcasing its broad applicability to complex steroid structures.