Expedited access to polyunsaturated fatty acids and biofunctional analogues by full solid-phase synthesis

Abstract

Polyunsaturated fatty acids (PUFAs) represent a fundamental and essential class of lipids that exhibit versatile biofunctions. Lipidomic analysis has identified a growing number of lipid species, including PUFAs with diverse structural variations and biofunctions, yet their structure–function relationships are still largely unknown. In this context, an efficient synthesis of PUFAs would be highly desirable. However, no practical methodology exists for their preparation, in contrast to peptides and nucleic acids, for which diverse molecules are accessible through a well-established solid-phase synthesis. To address this, we have developed an efficient and expedited method to access a wide array of PUFAs by full solid-phase synthesis. The method allows the synthesis of various PUFAs and analogues through rapid and facile operations. Moreover, within our PUFA library, we have discovered an artificial fatty acid, antiefin, that has a high anti-inflammatory effect in vivo. Therefore, our practical synthetic pathway to PUFAs, a crucial class of lipids, is expected to make an important contribution to lipid science.