Total Synthesis of a Marine Macrolide Natural Product, Iriomoteolide-2a: The Fundamental Role of Total Synthesis in Natural Product Chemistry

Marine macrolide natural products are an important source of new chemotherapeutics and their lead compounds. Although in recent years significant advances of NMR instruments have enabled structure determination of natural products at sub-microgram scale, complex macrolides are still challenging targets for structure assignment because many of them contain multiple stereogenic centers along conformationally flexible macrocyclic backbone. Accordingly, total synthesis plays a conclusive role in structure determination of complex macrolides. Furthermore, biological assessment of synthetic material is indispensable for validating the biological activity/potency of natural products. In this paper, we delineate our total synthesis of a marine macrolide iriomoteolide-2a as a case study that demonstrates the significance of total synthesis in natural product chemistry.