An efficient and novel method for the synthesis of cardiolipin and its analogs

A novel synthetic method has been developed for cardiolipin and its analog via a chlorophosphoramidite coupling reaction followed by oxidation. The reagent, N,N‐diisopropylmethylphosphoramidic chloride, couples effectively with 1,2‐O‐dimyristoyl‐sn‐glycerol in the presence of an amidite activator to form a phosphoamidite intermediate, which then reacts with 2‐O‐benzylglycerol in the presence of a basic catalyst followed by in situ oxidation to give the corresponding protected cardiolipin. Deprotection of the protecting groups provides tetramyristoyl cardiolipin in good overall yield of 60%. The synthetic method is applicable to large‐scale synthesis of cardiolipin and various analogs with or without unsaturation for liposomal drug delivery.