Development of novel vitamin K derivatives and elucidation of their biological functions

近年来，维生素K具有一些新的生物学特性，包括作为某些核受体配体的功能和抑制癌细胞增殖的活性。在这项研究中，我们试图开发新的维生素K衍生物，以阐明维生素K的详细生物学功能，并将其应用于临床。基于我们的假设，即维生素K(菜籽酮)将被代谢以产生某些维生素K功能所需的活性物质，我们设计了在侧链末端带有极性官能团的衍生物。因此，我们开发了维生素K代谢物K酸I和K酸II的高效合成方法，并系统地合成了不同侧链长度的维生素K氧化衍生物。其中一些新的衍生物在体外抑制了一些癌细胞的增殖，并在体内显示了抗炎作用。

Recently, novel biological properties of vitamin K, including function as some nuclear receptor ligand and inhibitory activity of cancer cell proliferation. In this study, we examined to develop novel vitamin K derivatives in order to clarify the detailed biological functions of vitamin K and to apply them to clinical utility. Based on our hypothesis that vitamin K (menaquinones) would be metabolized to yield an active substance for some vitamin K functions, we designed the derivatives bearing an polar functional group at the terminal of the side chain. As a result, we developed the efficient synthetic method for vitamin K metabolites, K acid I and II, and synthesized systematically the oxidative derivatives of vitamin K with various length of the side chain. Some of these novel derivatives inhibited the proliferation of some cancer cells in vitro, and showed anti-inflammatory effects in vivo.