天然有機化合物及び誘導体の合成とそれらを活用した生体機能の制御と理解

Abstract

Natural products are useful sources in the search for biochemical probes and drug leads because of their unique biological activities. However, synthetic studies or functional analyses of polycyclic complex natural products or conjugated lipids (e.g., glycolipids) are often hampered because of their synthesis and handling are challenging. On the basis of rational designs, synthetic studies, and chemical modifications, natural products need to be optimized to more potent compounds with improved activities, selectivities and/or physical properties. We have been synthesizing natural products and their derivatives for the elucidation of their biological mechanisms and discovery of drug leads. This review describes three topics for developing functional compounds derived from natural products for prospective involvement in pharmaceutical research: 1) direct construction of the ergot alkaloid scaffold by palladium catalyzed domino cyclization of amino allenes; 2) identification of novel sphingosine kinase inhibitors through a structure-activity relationship study of jaspine B; and 3) design, synthesis and biological evaluation of novel CD1d glycolipid ligands containing modified lipid moieties.