Stereocontrolled total synthesis of Resolvin D4 and 17(R)-Resolvin D4

The total synthesis of Resolvin D4 and its 17(R)-hydroxy-epimer is reported. These lipid-based natural products are biosynthesized from docosahexaenoic acid (DHA, C22:6) during the body's rapid cellular and chemical response to injurious stimuli and are part of a large class of bioactive molecules that resolve inflammation. Our convergent synthesis employed a chiral pool strategy starting from glycidol derivatives and d-erythrose to introduce stereogenic centers. A copper(i)-mediated cross coupling between propargyl bromide and terminal acetylenic precursors yielded core structures of late-stage key intermediates. A simultaneous Lindlar reduction of the skipped diynyl moiety followed by silyl group cleavage securely completed the synthesis. The synthetic availability of these molecules helped further elucidate their stereoselective biofunctions.

Automated summary

The total synthesis of Resolvin D4 and its 17(R)-hydroxy-epimer is reported. These molecules are biosynthesized from DHA and are bioactive molecules that can resolve inflammation. The synthesis of these molecules helps to further understand their biological functions.