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.

从新西兰的Latrunculia du Bocage海绵中分离出迪斯roh虫生物碱（Discorhabdin A-D），并对肿瘤细胞表现出极端的毒性（P388和L2110白血病）。这些新颖的分子具有独特的分子骨骼，其中融合了Azacarbocyclic dibromospirohexadienone系统和高度氧化的吲哚系统，其中色氨酸侧链被循环到吲哚喹酮上。最近，人们对这些具有挑战性的目标的总合成已引起了很多关注。作为我们对高空碘化学的持续研究的一部分，我们通过使用电子偏见和富含电子氨基氨基酮的氧化酚衍生物的氧化耦合反应，建立了通往阿扎卡核细胞螺旋二烯酮系统的一般途径。该方法应用于DiscorhabdinC的第一个总合成。在此合成过程中，还开发了一种新的有效方法。对其他Discorhabdin生物碱（a，b，d）的合成研究也开发出来，它们在分子中仍具有新的键合，包括一种新的构建方法，这些键仍具有新的键合，这些键仍在构造中。