Semisynthesis of the Neuroprotective Metabolite, Serofendic Acid

Serofendic acid is a natural neuroprotective molecule found in fetal calf serum. It is able to protect neurons against mechanisms of cell death associated with neurodegenerative disease. Because only trace quantities are present in fetal calf serum and complete chemical syntheses are long and inefficient, its development as a therapeutic agent has been slow. We engineered a heterologous metabolic pathway in Streptomyces to produce a late-stage synthetic intermediate, ent-atiserenoic acid, at high titers. We completed the total synthesis of serofendic acid from this intermediate in four steps.