A NEW DEVELOPMENT OF SYNTHETIC ORGANIC CHEMISTRY FOR BIOLOGICALLY ACTIVE NATURAL PRODUCTS OF MARINE ORIGINS

海洋生物活性天然产品合成有机化学的新进展

• 批准号: 10308027
• 负责人: MURAI Akio
• 金额: $ 21.18万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10308027/
• 关键词: (+)-obtusenyne; condensed polycyclic ether; ciguatoxin; total synthesis; polycavernoside A; pinnatoxins; pectenotoxins; epoxy alcohol; ランタントリフレート; 貝毒; Diels-Alder反応; 中員環エーテル; 環状ポリエーテル; 生合成; 超微量海産毒; ラクトンビニルトリフレート法; オブツセニン; 含臭素中員環エーテル

1) The first total synthesis of (+)-obtusenyne isolated from a red alga, Laurencia obtusa, has been achieved. Furthermore, two isomers of obtusenyne, which had been isolated by None and undetermined stereochemically, were totally synthesized. These results led to establishment of the absolute configuration of these compounds.2) The synthetic route has been established toward realization of the proposed biosynthetic pathway for condensed cyclic polyether compounds of marine sources. Eventually, construction of the condensed bicyclic and tricyclic ether compounds were carried out firstly in endo-fashions starting from the corresponding polyepoxy alcohols as the models.3) Two new efficient methods have been established in order to construct convergently two-condensed cyclic ethers.4) The synthetic studies were developed toward the total synthesis of ciguatoxin which is the causative compound for ciguatera intoxication. The synthetic strategy was based on the convergent procedure to synthe … More size the four respective fragments and then to combine them constructing three residual 6-7-membered cyclic ether systems (CD,GH,JK). The synthesis of the CD and JK ring systems has been already achieved.5) The first total synthesis of polycavernoside A isolated from a red alga, Polycavernosa tsudai, regarding as a causative compound for human intoxication, has been achieved. Furthermore, the structure-biological activity relationship has been clarified.6) The study toward the total synthesis of pinnatoxins causing shell-fish poisoning originated from Pinna attenuata has been developed. Resultingly, the 1-step construction of the common BCDEF-ring system has been achieved. Furthermore, the strategy for construction of the AG-ring system has been established using an intermolecular Diels-Alder reaction by the model experiments.7) The study toward the total synthesis of pectenotoxins causing shell-fish poisoning originated from Patinopecten yessoensis has been developed. Resultingly, all the fragments were able to be constructed except the C30 position. Less

1)首次实现了从一种红色植物Laurencia obtusa中分离得到的（+）-obtusenyne的全合成。在此基础上，全合成了两个由None分离得到的立体化学性质尚未确定的钝烯炔异构体。这些结果导致这些化合物的绝对构型的建立。2）为实现海洋来源的稠环聚醚化合物的生物合成途径建立了合成路线。最终，以相应的多环氧醇为模型化合物，首次以内消旋方式构建了稠合的双环和三环醚类化合物; 3）建立了两种新的有效的方法来构建收敛的双稠合环醚; 4）对引起雪卡毒素中毒的雪卡毒素进行了全合成研究。该合成策略基于收敛过程来合成 ...更多信息 将四个各自的片段进行大小调整，然后将它们联合收割机组合，构建三个残留的6-7元环醚系统（CD、GH、JK）。CD和JK环系统的合成已经完成。5）首次全合成了从被认为是人类中毒的致病化合物的红色珊瑚虫（Polycavernosa tsudai）中分离的polycavernoside A。6）开展了引起贝类中毒的江豚毒素的全合成研究。从而实现了一步构造通用BCDEF环系统。通过模型实验，建立了分子间Diels-Alder反应构建AG环体系的策略。7）开展了虾夷扇贝毒素的全合成研究。结果，除了C30位置之外，所有片段都能够被构建。少

项目成果

K.Fujiwara: "Novel Oxepane Formation by TiCl_4-Catalyzed Nucleophilic Cleavage of 1-Alkoxymethyl-6,8-dioxabicyclo[3.2.1]octanes"Tetrahedron. 56・8. 1065-1080 (2000)

K. Fujiwara：“TiCl_4 催化 1-烷氧基甲基-6,8-二氧杂双环[3.2.1]辛烷的亲核裂解形成新的氧杂环己烷”Tetrahedron 56·8 (2000)。

K. Fujiwara: "A Simple Convergent Method for the Construction of Fused Tri- and Tetracyclic Ether"Synlett. No.7. 1037-1040 (1999)

K. Fujiwara：“构建稠合三环和四环醚的简单收敛方法”Synlett。

T. Sugimoto: "Synthesis of the B, C, D, E, F-Ring Fragment of Pinnatoxins"SYNLETT. No.5. 541-544 (1999)

T. Sugimoto：“Pinnatoxins 的 B、C、D、E、F 环片段的合成”SYNLETT。

K.Fujiwara: "Total Synthesis of (+)-Obtusenyne"J.Org.Chem.. 64・8. 2616-2617 (1999)

K.Fujiwara：“(+)-Obtusenyne 的全合成”J.Org.Chem.. 64・8 (1999)。

L.Barriault: "Synthesis and Biological Evaluation of Analogues of the Marine Toxin Polycavernoside A"Bioorg.Med.Chem.Lett.. No.9. 2069-2072 (1999)

L.Barriault：“海洋毒素多海绵糖苷 A 类似物的合成和生物学评价”Bioorg.Med.Chem.Lett. 第 9 期。