Abstract The total and stereospecific syntheses of iPF 4α-VI and d 4-iPF 4α-VI have been accomplished. iPF 4α-VI is a docosahexanenoic acid (DHA)-derived isoprostane. DHA is the most abundant polyunsaturated fatty acid in the brain. Different synthetic designs have been used for the two syntheses. In the d 4-iPF 4α-VI design, the deuterated part of the molecule was introduced last in the synthesis.