Synthesis of new analogues based on fat-soluble vitamins and biological evaluation as therapeutic agents for degenerative disease of the brain

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We focused on vitamin K analogues among fat-soluble vitamins to explore therapeutic agents for degenerative disease of brain. It has been clarified that menaquinone-4 (MK-4), one of the vitamin K homologues, is biosynthesized in a living body and accumulated to the various tissues. MK-4 also protected oligodendrocyte precursors and immature fetal cortical neurons from oxidative injury, independent of the vitamin K-dependent γ-carboxylative reaction. Therefore, MK-4 should play an important role for a living body, especially in brain. On the basis of these findings, we evaluated the biological action of vitamin K homologues with chemical techniques using fluorescent labeled and deuterated labeled analogues. Furthermore, we also synthesized new vitamin K analogues and evaluated biological activities such as their differentiation-inducing activity from stem cells to neuron and gene transcription through the steroid and xenobiotic receptor (SXR).