24 マジンドリンA,Bの効率的不斉全合成と作用機作の解明(口頭発表の部)

概要

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Interleukin 6 (IL-6) is a multifunctional cytokine that acts on immune response, hematopoiesis and the nervous system. Thus, IL-6 plays one of the central regulatory roles in host defense mechanisms. However, it has been demonstrated that IL-6 produced by tumor cells causes cancer cachexia, and also stimulates the proliferation of tumor cells in an autocrine/paracrine manner. Therefore, it may be possible that the inhibition of IL-6 activity relieves cancer cachexia and suppress the growth of IL-6 dependent tumor cells. In the course of a search for inhibitors of IL-6 activity obtained from microoragnisms, madindoline A (MDL-A) and B (MDL-B) were discovered from the fermentation broth of Streptomyces nitrosporeus K93-0711. We previously described the determination of the complete absolute stereochemistries of MDL-A and B and the first total syntheses of these materials. We describe here more efficient total synthesis (second generation) via stereoselective acylation of ester by coordination with 3a-hydroxyfuroindoline moiety as the chiral ligand, and the intramolecular acylation of allylsilane. When we also prepared [^3H]-madindoline A, we clarified that [^3H]-madindoline A binds to gp-130, selectively. Moreover, madindoline A inhibited the differentiation of osteoblast cells.
天然有機化合物討論会の論文
2001-09-01