Synthetic Studies on Antitumor Marine Natural Products, Discorhabdin Alkaloids, and Their Congeners

discorhabdin生物碱（discorhabdin A-D）从新西兰Latrunculia du Bocage海绵中分离得到，对肿瘤细胞（P388和L2110白血病）具有极强的毒性。这些新分子具有独特的分子骨架，包括一个氮杂碳环二溴螺己二烯酮系统和一个高度氧化的吲哚系统，其中色胺侧链环化到吲哚醌上。近年来，这些具有挑战性的靶点的全合成受到了广泛关注。作为我们对高价碘化学的持续研究的一部分，我们已经建立了一个通用的途径，通过在对位上含有贫电子和富电子氨基醌的o -硅基化苯酚衍生物的氧化偶联反应，以苯基吡啶（III）双（三氟乙酸酯）（PIFA）为原料，得到氮杂环螺旋二烯酮体系。该方法首次应用于二溴甲醚c的全合成，同时也为氨基吲哚醌-亚胺体系的合成开辟了一条新的有效方法。对分子中具有硫醚键的其他二叉生物碱（A，B，D）的合成研究仍在进行中，包括一种新的合成方法的开发，以形成光学活性硫醚键。

The discorhabdin alkaloids (discorhabdin A-D) were isolated from the sponge of Latrunculia du Bocage in New Zealand and exhibit extreme toxicity toward tumor cells (P388 and L2110 leukemia). These novel molecules have a unique molecular skeleton incorporating an azacarbocyclic dibromospirohexadienone system and a highly oxidized indol system in which the tryptamine side chain is cyclized onto an indoloquinone. Recently, much attention has been paid to the total synthesis of these challenging targets. As a part of our continuous studies on hypervalent iodine chemistry, we have established a general route to the azacarbocyclic spiro dienone systems by an oxidative coupling reaction of the O-silylated phenol derivatives bearing both electron-poor and electron-rich aminoquinones at the para position, using phenyliodine(III) bis(trifluoroacetate)(PIFA). This method was applied to the first total synthesis of discorhabdin C. During this synthesis, a new effective method for the aminoindoloquinone imine systems was also developed.The synthetic studies of the other discorhabdin alkaloids (A,B,D), which have the thioether bonds in the molecule are still on line, including development of a new synthetic method for the optically active thioether bond formation.