Efficient and expedited access to polyunsaturated fatty acids and biofunctional analogs by full solid-phase synthesis

Polyunsaturated fatty acids (PUFAs) represent a fundamental and essential lipid class, exhibiting versatile biofunctions. Lipidomic analysis has identified a growing number of lipid species, including PUFAs with diverse structural variations and biofunctions, yet the structure–function relationships are still largely unknown. In this context, there is a long-sought demand to synthesize various PUFAs efficiently. However, no practical methodology exists, unlike the case with peptides and nucleic acids, where diverse molecules are accessible through a well-established solid-phase synthesis. Herein, we report an efficient and expedited method to access a wide array of PUFAs by full solid-phase synthesis. This method allows the synthesis of various PUFAs and analogs in rapid and facile operations. Moreover, we have discovered an artificial fatty acid, Antiefin, with a high anti-inflammatory effect in vivo within our PUFA library. This report provides a practical synthetic pathway for PUFAs, a crucial lipid class, expected to contribute to lipid science.