Synthesis and Application of Immunomodulatory Natural Products

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  • 天然化合物を基盤とした免疫調節性分子の合成と展開

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<p>In recent years, as the immunomodulatory mechanisms have been greatly elucidated, examples of selective immunomodulatory actions have been found for a wide variety of small-molecule compounds, including natural products. In particular, with regard to immune activation through inhibition of immunosuppressive molecules, which has been the focus of recent attention, research on inhibitors of enzymatic immunosuppressive molecules has focused on small molecules. On the other hand, it is important to understand the molecules derived from microorganisms that activate or suppress the immune system, for understanding the mechanisms of infection or the protection against the microbes. This group of molecules is also a treasure trove of diverse immunomodulatory structures. In this article, we introduce the development of synthetic methods for immunomodulatory molecules based on natural compounds and their related compounds. Firstly, the development of IDO1 inhibitors, which are attracting attention as targets for anti-tumor agents by inhibiting immunosuppressive molecules, based on longamide B, a natural product derived from marine sponges, was introduced. In the latter half, the synthesis and development of the selective immune modulatory compounds, based on microbial innate immune receptor ligands. are introduced. The compounds include 1,7-bisphosphate heptose (HBP) as a novel factor involved in innate immune activation via TIFA, and also inositol phospholipids (EhPIb from Entamoeba histolytica and Ac1PIM1 from Mycobacterium tuberculosis) involved in regulating immune mechanisms were described with the characteristic methods of phosphate introduction.</p>

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