Synthesis of Bioactive Anthraquinones Using Intramolecular

近年来，含有蒽醌骨架的化合物被报道具有许多有趣的活性，如神经元细胞保护活性（espicufolin）、抗帮助活性（AH-1763 IIa）和碳清除活性（SS43405E）。我们不仅计划制备具有生物活性的蒽醌类化合物及其类似物，而且还计划通过阐明它们对神经元细胞的体内作用机制来制备具有高活性的化合物。在本研究中，我们完成了蛇皮虫苷的合成和绝对结构的确定，SS43405E的合成和绝对结构的确定，并建立了以K1115A为代表的二羟基蒽醌类化合物的合成路线。用小鼠胚胎神经细胞对外消旋体和s -哌嗪苷进行了生物测定。对谷氨酸的毒性没有保护作用，但对细胞的毒性较弱。在抗助剂AH-1763 IIa的合成方法中，研究了两种不同的合成途径，但尚未实现全合成。现拟采用不对称醛醇缩合法制备AH-1763 IIa侧链。

Recently, compounds with an anthraquinone skeleton have been reported to have many interesting activities such as neuronal cell-protecting activity (espicufolin), anti-helpetic activity (AH-1763 IIa), and carbon clearance activity (SS43405E). We planned not only to prepare the bioactive anthraquinones and their analogs, but also to create highly active compounds by elucidation of their in vivo action mechanisms on neuronal cells.In this research, we achieved the synthesis and absolute structure determination of espicufolin, the synthesis and absolute structure determination of SS43405E, and establishment of the synthetic routes to dihydroxyanthraquinones represented by K1115A. Racemic and S-espicfolins were subject to bioassay by using mouse embryonic neuronal cells. The espicufolins showed no protecting activity for the toxicity of glutamate but weak cytotoxiciry to the cells employed. In the synthetic approach for antihelpetic AH-1763 IIa, two different routes were examined, but total synthesis has not been achieved, yet. We now intended to prepare the side chain of AH-1763 IIa by asymmetric aldol condensation.