We report a gram-scale total synthesis of protectin DX (PDX) following a convergent synthetic route (24 steps) from l-malic acid. This novel synthetic strategy is based on the assembly of three main building blocks using a Sonogashira coupling reaction (blocks A and B) and Wittig olefination (block C) to provide the 22-carbon backbone of PDX. A key stereoselective reduction of enediyne leads to a central E,Z,E-trienic system of PDX and also gives access to its labeled versions (D and T).