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

抗肿瘤海洋天然产物Discorhabdin生物碱及其同系物的合成研究

基本信息

批准号：
03670999
负责人：
KITA Yasuyuki
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670999/
关键词：
discorhabdin antitumor activity marine natural Product total synthesis hypervalent iodine reagent aminoindoloquinone imine system azacarbocyclic spiro dienone system discorhabdin

项目摘要

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.

discorhabdin 生物碱 (discorhabdin A-D) 是从新西兰 Latrunculia du Bocage 的海绵中分离出来的，对肿瘤细胞（P388 和 L2110 白血病）表现出极大的毒性。这些新型分子具有独特的分子骨架，包含氮杂碳环二溴螺己二烯酮系统和高度氧化的吲哚系统，其中色胺侧链环化到吲哚醌上。最近，这些具有挑战性的目标的全合成受到了广泛关注。作为我们对高价碘化学持续研究的一部分，我们通过对位带有贫电子和富电子氨基醌的O-甲硅烷基化苯酚衍生物的氧化偶联反应，建立了氮杂碳环螺二烯酮系统的一般路线，使用苯基碘(III)双(三氟乙酸酯)(PIFA)。该方法首次应用于discorhabdin C的全合成。在该合成过程中，还开发了一种新的有效的氨基吲哚醌亚胺体系的方法。其他具有硫醚的discorhabdin生物碱（A、B、D）的合成研究分子中的键仍然在线，包括开发一种用于光学活性硫醚键形成的新合成方法。