Synthetic Studies on Aplysiatoxin and Its Analogues

海兔毒素及其类似物的合成研究

• 批准号: 01571170
• 负责人: OKADA Kunisuke
• 金额: $ 1.09万
• 依托单位: Faculty of Pharmacy, Meijo 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: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01571170/
• 关键词: Tumor Promoter; Aplysiatoxin; Marine Natural Products; Marine Toxin; Total Synthesis; Macrolactone

This work was undertaken to develop a method for the synthesis of Aplysiatoxin (I), a marine natural product exhibiting a tumor promoting activity very similar to that of the better known TPA and teleocidines. We have also interested in a synthesis of newly designed tomor promoters from (I) in future. Aplysiatoxin (I) includes a 14-membered bis-lactone chromophore at C_1, C_<29> and C_9, C_<27>, phenolic moiety at C_<15>, and 9 chiral centers on a acyclic parts of C_1-C_<15> and C_<27>-C_<31>.Our synthetic strategy toward (I) involves 1) retrosynthetic disconnection into three segments A (C_8-C_<15>), B (C_2-C_7), and C including acethyene moiety (C_1, C_<27>-C_<31>) ; 2) synthesis of all segments in optically pure form, starting from (+)-Tartaric acid, (-)-Tartaric Acid, and (-)-Threonine, respectively ; 3) coupling the segment A with B followed by A-B with acetylenic part C ; 4) a novel transformation of acyclic precursor shown as the segment [A-B-C] into (C_9, C_<27>)-seco acid; 5) lactonization of C_9-hydroxy group and C_<27>-carboxylic acid by using the macrolactonization method developed by Masamune and coworkers. The final lactonization is still unsuccessful and is now being conducted.

这项工作的目的是开发一种合成海兔毒素 (I) 的方法，海兔毒素 (I) 是一种海洋天然产物，具有与广为人知的 TPA 和 teleocidines 非常相似的肿瘤促进活性。我们还对未来从 (I) 合成新设计的 tomor 启动子感兴趣。海螺毒素 (I) 包括 C_1、C_<29> 和 C_9、C_<27> 处的 14 元双内酯发色团、C_<15> 处的酚部分以及 C_1-C_<15> 和 C_<27>-C_<31> 的无环部分上的 9 个手性中心。我们针对 (I) 的合成策略包括 1) 逆向合成断线成三 [0101] 包含乙炔部分的链段A(C_8-C_<15>)、B(C_2-C_7)和C(C_1、C_<27>-C_<31>)； 2) 分别从(+)-酒石酸、(-)-酒石酸和(-)-苏氨酸开始合成光学纯形式的所有片段； 3)将链段A与B偶联，然后将A-B与炔属部分C偶联； 4)将片段[A-B-C]所示的无环前体新颖地转变为(C_9，C_27)-seco酸； 5)利用Masamune及其同事开发的大内酯化方法对C_9-羟基和C_27-羧酸进行内酯化。最终的内酯化反应仍未成功，目前正在进行中。

项目成果

Kunisuke Okada,: "SYNTHETIC STUDIES ON APLYSIATOXIN. INTRAMOLECULAR ESTER FORMATION FROM 3ーACETOXYFURAN DERIVATIVE VIA OXIDATIVE RING OPENING REACTION" Heterocycles. 32. (1991)

Kunisuke Okada，：“海螺毒素的合成研究。通过氧化开环反应从 3-乙酰氧基呋喃衍生物形成分子内酯”32。（1991）

Kunisuke Okada: "Synthetic Studies on Aplysiatoxin. Intramolecular Ester Formation from 3-Acetoxyfuran Derivative Via Oxidative Ring Opening Reaction." Heterocycles. 32. No. 3 (1991)

Kunisuke Okada：“海兔毒素的合成研究。通过氧化开环反应从 3-乙酰氧基呋喃衍生物形成分子内酯。”