A Concise and Efficient Synthesis of 25( S )-Δ ⁷ -Dafachronic Acid, a Lead Compound for the Development of Antiparasitic Agents

High Resolution Image Download MS PowerPoint Slide 25( S )-Δ 7 -Dafachronic acid is the endogenous ligand of the nuclear receptor DAF-12 and a key chemical probe for the discovery and development of new anthelmintic agents. Reliable access to multigram quantities of this natural steroid is crucial to enable chemical biology studies, improved analogue synthesis, and in vivo evaluations. Herein, we report the optimization of an eight-step synthetic route to 25( S )-Δ 7 -dafachronic acid from renewable, inexpensive, and readily available ergosterol, delivering the target compound in 44% overall yield on a multigram scale. Key process features include side chain oxidative cleavage via ozonolysis reaction and telescoping of the resulting C22-aldehyde into a Horner–Wadsworth–Emmons olefination without intermediate purification. A comparative assessment using process-relevant metrics, including safety, efficiency, and sustainability, demonstrates the superior performance of this route compared to previously reported synthetic approaches. Overall, this synthesis provides a practical and scalable access to 25( S )-Δ 7 -dafachronic acid for biological investigations and medicinal chemistry studies toward new antiparasitic agents.