A short, concise route to diphosphatidylglycerol (Cardiolipin) and its variants

A new approach is described for the synthesis of the cardiolipin family of phospholipids that uses phosphonium salt methodology. The method involves the reaction of 2‐O‐protected glycerol with a trialkyl phosphite derived from 1,2‐diacyl‐sn‐glycerol in the presence of pyridinium bromide perbromide and triethylamine to afford the phosphoric triesters. The synthesis involves three steps and allows the preparation of a wide range of cardiolipins with different substitution patterns and chain lengths, including unsaturated derivatives. The use of inexpensive protecting groups and the ease of purification facilitate this synthetic route and allow its scale‐up in a higher overall yield (72%) than the literature methods.