First stereoselective total synthesis of 4(),5()-oxido-17()-hydroxy-6(),8(),10(),13(),15(),19()-docosahexaenoic acid, the biosynthetic precursor of resolvins D3 and D4.

The first total convergent synthesis of 4(),5()-oxido-17()-hydroxy-6(),8(),10(),13(),15(),19()-docosahexaenoic acid (1) is described. The reported synthesis led to confirmation of the native epoxydocosahexaenoic acid as the biosynthetic precursor of lipid mediators resolvin D3 and resolvin D4. These potent enzymatic products of docosahexaenoic acid (DHA) are important signaling molecules in the resolution of inflammation.